Metformin and blood pressure -
Circ Res. Kassan M, Galán M, Partyka M, Saifudeen Z, Henrion D, Trebak M, et al. Endoplasmic reticulum stress is involved in cardiac damage and vascular endothelial dysfunction in hypertensive mice.
Duan Q, Song P, Ding Y, Zou MH. Activation of AMP-activated protein kinase by metformin ablates angiotensin II-induced endoplasmic reticulum stress and hypertension in mice in vivo. Br J Pharmacol. Hamidi Shishavan M, Henning RH, van Buiten A, Goris M, Deelman LE, Buikema H.
Metformin improves endothelial function and reduces blood pressure in diabetic spontaneously hypertensive rats independent from glycemia control: comparison to vildagliptin.
Sci Rep. Verma S, Bhanot S, McNeill JH. Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats. Am J Physiol. CAS PubMed Google Scholar.
Zhou L, Liu H, Wen X, Peng Y, Tian Y, Zhao L. Effects of metformin on blood pressure in nondiabetic patients: a meta-analysis of randomized controlled trials. Okada K, Minamino T, Tsukamoto Y, Liao Y, Tsukamoto O, Takashima S, et al.
Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis.
Cheang WS, Tian XY, Wong WT, Lau CW, Lee SS, Chen ZY, et al. Hwang SL, Jeong YT, Li X, Kim YD, Lu Y, Chang YC, et al. Inhibitory cross-talk between the AMPK and ERK pathways mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle.
Kim A, Im M, Ma JY. Hu L, Zhou L, Wu X, Liu C, Fan Y, Li Q. Int J Clin Exp Pathol. PubMed PubMed Central Google Scholar. Li J, Wang Y, Wang Y, Wen X, Ma XN, Chen W, et al. Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates endoplasmic reticulum stress-associated endothelial dysfunction.
J Mol Cell Cardiol. Jung TW, Lee SY, Hong HC, Choi HY, Yoo HJ, Baik SH, et al. AMPK activator-mediated inhibition of endoplasmic reticulum stress ameliorates carrageenan-induced insulin resistance through the suppression of selenoprotein P in HepG2 hepatocytes. Mol Cell Endocrinol. Yamamoto E, Kataoka K, Shintaku H, Yamashita T, Tokutomi Y, Dong YF, et al.
Novel mechanism and role of angiotensin II induced vascular endothelial injury in hypertensive diastolic heart failure. Davis BJ, Xie Z, Viollet B, Zou MH. Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase.
Tsai CM, Kuo HC, Hsu CN, Huang LT, Tain YL. Metformin reduces asymmetric dimethylarginine and prevents hypertension in spontaneously hypertensive rats. Transl Res.
Pitocco D, Zaccardi F, Tarzia P, Milo M, Scavone G, Rizzo P, et al. Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study. Diabetes Obes Metab. Katakam PV, Ujhelyi MR, Hoenig M, Miller AW.
Metformin improves vascular function in insulin-resistant rats. Laplante MA, Wu R, Moreau P, de Champlain J. Endothelin mediates superoxide production in angiotensin II-induced hypertension in rats. Free Radic Biol Med. Gumusel B, Tel BC, Demirdamar R, Sahin-Erdemli I. Reactive oxygen species-induced impairment of endothelium-dependent relaxation in rat aortic rings: protection by L-arginine.
Eur J Pharmacol. Konior A, Schramm A, Czesnikiewicz-Guzik M, Guzik TJ. NADPH oxidases in vascular pathology. Antioxid Redox Signal. An H, Wei R, Ke J, Yang J, Liu Y, Wang X. Metformin attenuates fluctuating glucose-induced endothelial dysfunction through enhancing GTPCH1-mediated eNOS recoupling and inhibiting NADPH oxidase.
J Diabetes Complicat. Piwkowska A, Rogacka D, Jankowski M, Dominiczak MH, Stepiński JK, Angielski S. Metformin induces suppression of NAD P H oxidase activity in podocytes. Download references. Department of Emergency and Critical Care, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
West Coast University, School of Pharmacy, Los Angeles, CA, , USA. California State University, Los Angeles, Los Angeles, CA, , USA. Cardiovascular Division, Department of Medicine, and Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, IA City, IA, , USA.
Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, , Korea. You can also search for this author in PubMed Google Scholar. Correspondence to Modar Kassan.
The original online version of this article was revised: Due to the presentation of Figure 6B was incorrect. Reprints and permissions. Chen, C. et al. Hypertens Res 42 , — Download citation. Received : 28 September Revised : 23 November Accepted : 20 December Published : 21 January Issue Date : July Anyone you share the following link with will be able to read this content:.
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nature hypertension research articles article. Download PDF. This article has been updated. Abstract Metformin is an antidiabetic drug. You have full access to this article via your institution. Empagliflozin maintains capillarization and improves cardiac function in a murine model of left ventricular pressure overload Article Open access 15 September Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway Article Open access 11 November Dapagliflozin attenuates pressure overload-induced myocardial remodeling in mice via activating SIRT1 and inhibiting endoplasmic reticulum stress Article 01 December Introduction Metformin, an oral antidiabetic agent, is usually prescribed as a first-line drug to patients with type-2 diabetes mellitus T2DM by international guidelines [ 1 ].
Materials and methods General protocol in mice All experiments were performed according to the guidelines of Animal Care Committee of Shanghai Jiao Tong University School of Medicine.
Western blot analysis Western blot analysis for total and phospho eNOS, phospho PERK, total and phospho eIF2-α, CHOP, GRP78, ATF6, and total and phospho AMPKα dilution, Cell Signaling Technology, Inc, USA was performed in lysates of mesenteric arteries as previously described.
Immunofluorescence MRA segments were frozen in Tissue Tek OCT embedding medium Sakura Finetek Europe, The Netherlands. Nicotinamide adenine dinucleotide phosphate NADPH oxidase activity assay Superoxide anion levels generated by NADPH oxidase activity were measured in lysates of aorta and MRA using lucigenin chemiluminescence.
Drugs Phenylephrine hydrochloride, acetylcholine, NADPH, angiotensin II, and metformin were obtained from Sigma—Aldrich USA. Results Metformin ameliorated angiotensin II-induced systolic blood pressure We aimed to study the effect of metformin on SBP.
Full size image. Discussion In the present study, we demonstrated that metformin inhibited Ang II-induced aberrant ER stress and vascular dysfunction through activation of AMPK. Similar content being viewed by others. References Pernicova I, Korbonits M. Article CAS Google Scholar Giugliano D, De Rosa N, Di Maro G, Marfella R, Acapora R, Buoninconti R, et al.
Article CAS Google Scholar He H, Zhao Z, Chen J, Ni y, Zhong J, Yan Z, et al. Article CAS Google Scholar Muntzel MS, Nyeduala B, Barrett S. Article CAS Google Scholar Cody RJ. Article CAS Google Scholar Ohishi M.
Article Google Scholar Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Article CAS Google Scholar Campbell DJ. Article CAS Google Scholar Hasty AH, Harrison DG. Article CAS Google Scholar Deji N, Kume S, Araki S, Isshiki K, Araki H, Chin-Kanasaki M, et al.
Article CAS Google Scholar Ford RJ, Rush JW. Article CAS Google Scholar Liang B, Wang S, Wang Q, Zhang W, Viollet B, Zhu Y, et al. Article CAS Google Scholar Dong Y, Zhang M, Liang B, Xie Z, Zhao Z, Asfa S, et al.
Article CAS Google Scholar Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Article CAS Google Scholar Kassan M, Ait-Aissa K, Radwan E, Mali V, Haddox S, Gabani M, et al.
Article CAS Google Scholar Kassan M, Galan M, Partyka M, Trebak M, Matrougui K. Article CAS Google Scholar Linden MA, Lopez KT, Fletcher JA, Morris EM, Meers GM, Siddique S, et al. Article CAS Google Scholar Cai H, Harrison DG. Article CAS Google Scholar Kassan M, Galán M, Partyka M, Saifudeen Z, Henrion D, Trebak M, et al.
Article CAS Google Scholar Duan Q, Song P, Ding Y, Zou MH. Article CAS Google Scholar Hamidi Shishavan M, Henning RH, van Buiten A, Goris M, Deelman LE, Buikema H. Article Google Scholar Verma S, Bhanot S, McNeill JH.
CAS PubMed Google Scholar Zhou L, Liu H, Wen X, Peng Y, Tian Y, Zhao L. Article CAS Google Scholar Okada K, Minamino T, Tsukamoto Y, Liao Y, Tsukamoto O, Takashima S, et al.
Chakraborty, S. Chowdhury, M. Bhattacharyya, Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. Diabetes Res. Pradhan, B. Everett, N. Cook, N. Rifai, P. Ridker, Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial.
JAMA 11 , — Caballero, A. Delgado, C. Aquilar-Salinas, A. Herrera, J. Castillo, T. Cabrera, F. Gomez-Perez, J. Rull, The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial.
Selvin, S. Bolen, H. Yeh, C. Wiley, L. Wilson, S. Marinopoulos, L. Feldman, J. Vassy, R. Wilson, E. Bass, F.
Brancati, Cardiovascular outcomes in trials of oral diabetes medications. A systematic review. Article PubMed PubMed Central Google Scholar. Fitch, S. Abbara, H. Lee, E. Stavrou, R. Sacks, L. Hemphill, M. Torriani, S. Grinspoon, Effects of lifestyle modification and metformin on atherosclerotic indices among HIV-infected patients with the metabolic syndrome.
AIDS 26 , — Bulcão, F. Ribeiro-Filho, A. Sañudo, S. Roberta Ferreira, Effects of simvastatin and metformin on inflammation and insulin resistance in individuals with mild metabolic syndrome.
Drugs 7 3 , — Ladeiras-Lopes, R. Fontes-Carvalho, N. Bettencourt, F. Sampaio, V. Gama, A. Leite-Moreira, Novel therapeutic targets of metformin: metabolic syndrome and cardiovascular disease.
Expert Opin. Targets 19 7 , — Preiss, S. Lloyd, I. Ford, J. McMurray, R. Holman, P. Welsh, M. Fisher, C. Packard, N. Sattar, Metformin for non-diabetic patients with coronary heart disease the CAMERA study : a randomised controlled trial.
Lancet Diabetes Endocrinol. Aguiar, L. Bahia, N. Villela, C. Laflor, F. Sicuro, N. Wiernsperger, D. Bottino, E. Bouskela, Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance.
Diabetes Care 29 5 , — Download references. Postgraduate Program in Medicine: Cardiology, School of Medicine, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
Division of Cardiology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Postgraduate Program in Medicine: Endocrinology, School of Medicine, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. You can also search for this author in PubMed Google Scholar.
Correspondence to Vicente Corrêa Júnior. Reprints and permissions. Júnior, V. et al. Effect of metformin on blood pressure in patients with hypertension: a randomized clinical trial. Endocrine 63 , — Download citation.
Received : 31 May Accepted : 12 August Published : 21 August Issue Date : 15 February Anyone you share the following link with will be able to read this content:.
Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Abstract Objective Part of the beneficial effects of metformin on the prevention of cardiovascular events in diabetes can be attributed to pleiotropic effects, including a blood pressure BP -lowering effect.
Results The sample consisted mainly of White overweight women. Conclusion In the present trial, metformin did not reduce BP, measured by ABP monitoring, in hypertensive patients without diabetes. Access this article Log in via an institution.
References World Health Organization. int W. JAMA , — Article CAS PubMed Google Scholar C. Circulation 12 , — Article PubMed Google Scholar R. BMJ , — Article PubMed Central Google Scholar Evidence-Based Guideline for the Management of High Blood Pressure in Adults, Report from the panel members appointed to the Eighth Joint National Committee JNC 8.
JAMA 5 , — Article CAS Google Scholar UK Prospective Diabetes Study UKPDS Group, Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes UKPDS Lancet , — Article Google Scholar C.
Nature , — Article CAS PubMed PubMed Central Google Scholar I. Hypertension 33 , — Article CAS PubMed Google Scholar M. Diabetes Care 16 , — Article CAS PubMed Google Scholar J. Diabetes Care 16 , — Article CAS PubMed Google Scholar D.
Diabetes Care 16 , — Article CAS PubMed Google Scholar K. Diabetes Care 33 , — Article CAS PubMed PubMed Central Google Scholar R. Atherosclerosis , — Article CAS PubMed Google Scholar A. JAMA 11 , — Article CAS PubMed Google Scholar A. AIDS 26 , — Article CAS PubMed Google Scholar C. Drugs 7 3 , — Article PubMed Google Scholar R.
Targets 19 7 , — Article CAS PubMed Google Scholar D. Diabetes Care 29 5 , — Article CAS PubMed Google Scholar Download references. Schaan Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Beatriz D. Schaan Authors Vicente Corrêa Júnior View author publications.
View author publications. Or, it might be because the drug is good for many different conditions: aspirin has often been called a wonder drug because it can relieve pain, treat or prevent cardiovascular disease, and even prevent cancer. Could metformin be joining this list? It's approved in the US to treat type 2 diabetes when used with diet and exercise by people ages 10 and older.
But in recent years, interest has grown regarding its potential to prevent or treat a variety of other conditions, including aging. Yes, aging. If that's true, "wonder drug" might be an understatement.
The history of metformin goes back hundreds of years. In Europe, the medicinal herb Galega officinalis was popular for digestive health and to treat urinary problems and other ailments. Then in , a scientist discovered that one of its ingredients, guanidine, could lower blood sugar.
Medicines containing guanidine, such as metformin and phenformin, were developed to treat diabetes. But they fell out of favor due to serious side effects caused by phenformin, and by the discovery of insulin.
Chrome Extension. Talk with us. Use Metfotmin ChatGPT. What blood pressure medicine should not be taken with metformin? Blood pressure. Diabetes mellitus. Type 2 diabetes. Thank you Brain training exercises visiting nature. You are using a browser version with bllood support for Pressurs. To pressuee the best experience, we recommend you use a more Metformin and blood pressure to Metformin and blood pressure browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Metformin confers vascular benefits beyond glycemia control, possibly via pleiotropic effects on endothelial function. In typediabetes-mellitus T1DM- patients metformin improved flow-mediated dilation but also increased prostaglandin PG -F 2αa known endothelial-contracting factor.Thank you for visiting nature. Presdure are Metforimn a browser version with prexsure support for CSS. To obtain the Metfprmin experience, we recommend you use Metdormin more up to Metgormin browser or turn off compatibility mode in Internet Explorer.
In the meantime, to presdure continued preasure, we are pressurs the site bliod styles and JavaScript. A Metformin and blood pressure to this article was oressure on 30 September Metformin is an bllood Metformin and blood pressure. However, the pleiotropic beneficial effects of metformin in nondiabetic models still need Metformin and blood pressure Gluten-free bakery defined.
The objective of this study ptessure to investigate the effect of metformin on angiotensin Pressute Ang II Waist to hip ratio hypertension and cardiovascular lressure.
Mice infused with angiotensin II peessure an increase in blood pressure associated with enhanced vascular endoplasmic reticulum ER stress markers, which were blunted after metformin treatment. Renewable energy certifications, hypertension-induced Metfrmin in phosphorylated AMPK, endothelial nitric oxide synthase eNOs phosphorylation, and endothelium-dependent relaxation EDR in mesenteric prwssure arteries MRA were rescued after pressude treatment.
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Preszure these factors were reversed subsequently with metformin treatment. ER stress presaure by metformin improves Metformun function in hypertension. Therefore, metformin could be Metformjn potential therapy for cardiovascular lbood in hypertension independent of its effects on diabetes.
Masaaki Nakao, Ippei Bloor, … Tohru Minamino. Roberto Palacios-Ramírez, Raquel Hernanz, … María J. Metformin, an oral antidiabetic Metgormin, is usually Metcormin as a first-line drug to nlood with Carbohydrate metabolism and insulin sensitivity diabetes mellitus T2DM by international guidelines [ 1 ].
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Thus, the molecular mechanisms that determine the effect of metformin on blood vessel responsiveness in relation xnd lowering blood anv remain uncharacterized. The renin—angiotensin—aldosterone system Metfomrin has a central role in vascular adaptive vlood [ 5 blkod. The Metformin and blood pressure of this system has been demonstrated in a range of cardiovascular bloox, especially in hypertension and hypertension with eMtformin mellitus [ 6 ].
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Hydration and immune function in youth athletes endothelial cells ECsNutrition for martial arts deficiency Metformin and blood pressure aberrant ER prrssure resulting in vascular dysfunction and atherosclerosis in vivo [ 13 ].
Published data indicate that metformin is a potent activator of AMPK [ 14 ]. The aim of the present study is to determine whether AMPK-suppressed ER stress by metformin is required to preserve endothelial function in an Ang II-induced hypertension model.
All experiments were performed according to the guidelines of Animal Care Committee of Shanghai Jiao Tong University School of Medicine. Body weight was recorded weekly during the experimental period. The dose of Ang II was selected based on our previous studies [ 1516 ], and the dose of metformin used was based on the literature [ 17 ].
Systolic blood pressure SBP was measured using the CODA tail-cuff blood pressure system Kent Scientific Torrington, USA. Arterial blood pressure measurements were performed at the same time of day between 9 and 11 a. to avoid the influence of the circadian cycle.
SBP was obtained by calculating the average of 10 measurements. At the end of the treatment period, mice were anesthetized with isoflurane. Mesenteric resistance arteries MRA were then harvested immediately and placed in PSS solution composition in mM: NaCl ; KCl 4.
Systolic blood pressure was measured weekly during the treatment period. At the end of treatment, mice were anesthetized with isoflurane, and then mesenteric resistance arteries were immediately harvested and placed in PSS solution for reactivity and biochemistry assays.
MRA were mounted in a small vessel dual-chamber myograph for measurement of isometric tension. After a 1-h incubation, cumulative concentration responses to phenylephrine PE, 3. Western blot analysis for total and phospho eNOS, phospho PERK, total and phospho eIF2-α, CHOP, GRP78, ATF6, and total and phospho AMPKα dilution, Cell Signaling Technology, Inc, USA was performed in lysates of mesenteric arteries as previously described.
MRA segments were frozen in Tissue Tek OCT embedding medium Sakura Finetek Europe, The Netherlands. Transverse sections were cut 5-μm thick. Immunofluorescent signals were viewed using an Eclipse 55i fluorescence microscope x20Nikon. Superoxide anion levels generated by NADPH oxidase activity were measured in lysates of aorta and MRA using lucigenin chemiluminescence.
Phenylephrine hydrochloride, acetylcholine, NADPH, angiotensin II, and metformin were obtained from Sigma—Aldrich USA. U and tunicamycin were obtained from Tocris Bioscience.
Concentration-response curves were analyzed using GraphPad Prism 4. We aimed to study the effect of metformin on SBP. Our data demonstrated that mice infused with Ang II for 2 weeks had significantly increased SBP compared to the sham group infused with saline Fig.
Interestingly, metformin treatment significantly reduced SBP in Ang II-infused mice Fig. Body weight was not affected by treatment and was similar among groups Fig. Metformin reduces systolic blood pressure and improves vascular function in hypertension. b Body weight BW was similar among groups.
c, d Contractile response to thromboxane analogue U and phenylephrine PE in mesenteric resistance arteries MRA was similar among groups. f Endothelial-independent relaxation to sodium nitroprusside SNP was similar among groups.
kg -1 body weight per day. To study the effects of metformin treatment on MRA reactivity, we subjected vessels to cumulative doses of thromboxane analogue U and PE. Our data indicate that there were no differences in the contractile response between the sham group and the groups infused with Ang II in the presence or absence of metformin Fig.
To determine the role of metformin in vascular endothelial dysfunction in hypertension, we examined EDR by using acetylcholine Ach. Ang II-induced hypertension attenuated EDR in MRA compared with the sham group Fig. Interestingly, metformin treatment significantly improved EDR Fig.
Endothelium-independent relaxation to SNP was similar among groups Fig. Since ACh produces NO through activation of eNOS, we analyzed the protein levels of total and phosphorylated eNOS. Our data indicate that Ang II-induced hypertension reduced eNOS phosphorylation in MRA, which was restored after metformin treatment Fig.
The expression of total eNOS protein level was similar among all groups of mice Fig. The aim of this experiment was to study the effect of metformin on AMPK kinase. Metformin treatment significantly reduced ER stress marker expression levels Fig.
Metformin alleviates hypertension-induced ER stress by activating AMPK. T-AMPK expression in MRA was similar among groups Fig. However, the expression of p-AMPK was significantly reduced after exposure to Ang II compared to the sham group.
p-AMPK expression was restored by treatment with metformin Fig. This experiment was performed to assess the effect of metformin on oxidative stress. Our results showed that NADPH oxidase activity was higher in the Ang II group compared to the sham group Fig.
Interestingly, metformin significantly reduced NADPH oxidase activity Fig. To confirm our data, we proceeded with an immunostaining experiment using von Willebrand factor vWF as a marker for blood vessel endothelial cells and 8-OHDG as a marker for oxidative stress.
Our data showed that 8-OHDG was significantly increased in the Ang II-infused mice compared to sham mice. Treatment with metformin significantly reduced expression of 8-OHDG Fig. Metformin inhibits oxidative stress. To further determine the relationship between metformin, ER stress, AMPK, and vascular dysfunction independent of hypertension, we performed in vivo studies by treating mice with an ER stress inducer tunicamycin for 2 weeks.
The results showed that treatment with tunicamycin had no effect on systolic blood pressure Fig. Metformin improves vascular function independent of hypertension. a Systolic blood pressure SBP was similar among groups and in the range of normotensive values.
b, c Contractile response to thromboxane analogue U and phenylephrine PE in mesenteric resistance arteries MRA was similar among groups. e Endothelial-independent relaxation to sodium nitroprusside SNP was similar among groups.
We did not detect any differences in contractile response to U or PE among groups Fig. EDR that was damaged after tunicamycin treatment was significantly improved with metformin treatment Fig. We then detected the expression of eNOS, and there was no difference in the expression of T-eNOS among groups Fig.
Phosphorylated eNOS was reduced in the tunicamycin mice compared to the sham mice. Interestingly, treatment with metformin completely restored the expression of p-eNOS Fig. The rationale of this experiment is to see the effect of metformin on vasculature independent of hypertension.
Our data showed that ER stress marker BIP, p-PERK, and CHOP expression levels in MRA were higher in the tunicamycin group compared to the sham group Fig.
Treatment with metformin significantly reduced ER stress marker expression levels Fig. Metformin alleviates tunicamycin-induced ER stress by activating AMPK.
: Metformin and blood pressure| Is metformin a wonder drug? - Harvard Health | To evaluate the association of nad genetically proxied prrssure of Pgessure drug targets on BP and All-natural fat burners of hypertension through a drug-target Presskre Randomization Blokd analysis. Get the most important Metformin and blood pressure stories of the day, free in your inbox. Metformin is a highly desirable therapy for T2DM for a number of reasons. Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy. Use only the brand of this medicine that your doctor prescribed. |
| See what other people are reading | Thus, metformin appears to improve vascular function independent of SBP. This study showed some of the beneficial pleiotropic effects of metformin independent of its effects on diabetes. In summary, we demonstrated that metformin, independent of changes in SBP, improves vascular endothelium-dependent relaxation, increases eNOS activation, and suppresses ER stress and NADPH oxidase activity by activating AMPK. These results suggest that activation of metformin could be a useful therapeutic strategy for reversing vascular complications and cardiac damage from hypertension. Pernicova I, Korbonits M. Metformin mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. Article CAS Google Scholar. Giugliano D, De Rosa N, Di Maro G, Marfella R, Acapora R, Buoninconti R, et al. Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care. He H, Zhao Z, Chen J, Ni y, Zhong J, Yan Z, et al. Metformin-based treatment for obesity-related hypertension: a randomized, double-blind, placebo-controlled trial. J Hypertens. Muntzel MS, Nyeduala B, Barrett S. High dietary salt enhances acute depressor responses to metformin. Am J Hypertens. Cody RJ. The sympathetic nervous system and the renin-angiotensin-aldosterone system in cardiovascular disease. Am J Cardiol. Ohishi M. Hypertension with diabetes mellitus: physiology and pathology. Hypertens Res. Article Google Scholar. Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci Usa. Campbell DJ. Do intravenous and subcutaneous angiotensin II increase blood pressure by different mechanisms? Clin Exp Pharmacol Physiol. Hasty AH, Harrison DG. Endoplasmic reticulum stress and hypertension—a new paradigm? J Clin Invest. Deji N, Kume S, Araki S, Isshiki K, Araki H, Chin-Kanasaki M, et al. Role of angiotensin II-mediated AMPK inactivation on obesity-related salt-sensitive hypertension. Biochem Biophys Res Commun. Ford RJ, Rush JW. Endothelium-dependent vasorelaxation to the AMPK activator AICAR is enhanced in aorta from hypertensive rats and is NO and EDCF dependent. Am J Physiol Heart Circ Physiol. Liang B, Wang S, Wang Q, Zhang W, Viollet B, Zhu Y, et al. Aberrant endoplasmic reticulum stress in vascular smooth muscle increases vascular contractility and blood pressure in mice deficient of AMP-activated protein kinase-α2 in vivo. Arterioscler Thromb Vasc Biol. Dong Y, Zhang M, Liang B, Xie Z, Zhao Z, Asfa S, et al. Reduction of AMP-activated protein kinase alpha2 increases endoplasmic reticulum stress and atherosclerosis in vivo. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. Kassan M, Ait-Aissa K, Radwan E, Mali V, Haddox S, Gabani M, et al. Essential Role of Smooth Muscle STIM1 in Hypertension and Cardiovascular Dysfunction. Kassan M, Galan M, Partyka M, Trebak M, Matrougui K. Linden MA, Lopez KT, Fletcher JA, Morris EM, Meers GM, Siddique S, et al. Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats. Appl Physiol Nutr Metab. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. Kassan M, Galán M, Partyka M, Saifudeen Z, Henrion D, Trebak M, et al. Endoplasmic reticulum stress is involved in cardiac damage and vascular endothelial dysfunction in hypertensive mice. Duan Q, Song P, Ding Y, Zou MH. Activation of AMP-activated protein kinase by metformin ablates angiotensin II-induced endoplasmic reticulum stress and hypertension in mice in vivo. Br J Pharmacol. Hamidi Shishavan M, Henning RH, van Buiten A, Goris M, Deelman LE, Buikema H. Metformin improves endothelial function and reduces blood pressure in diabetic spontaneously hypertensive rats independent from glycemia control: comparison to vildagliptin. Sci Rep. Verma S, Bhanot S, McNeill JH. Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats. Am J Physiol. CAS PubMed Google Scholar. Zhou L, Liu H, Wen X, Peng Y, Tian Y, Zhao L. Effects of metformin on blood pressure in nondiabetic patients: a meta-analysis of randomized controlled trials. Okada K, Minamino T, Tsukamoto Y, Liao Y, Tsukamoto O, Takashima S, et al. Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis. Cheang WS, Tian XY, Wong WT, Lau CW, Lee SS, Chen ZY, et al. Hwang SL, Jeong YT, Li X, Kim YD, Lu Y, Chang YC, et al. Inhibitory cross-talk between the AMPK and ERK pathways mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. Kim A, Im M, Ma JY. Hu L, Zhou L, Wu X, Liu C, Fan Y, Li Q. Int J Clin Exp Pathol. PubMed PubMed Central Google Scholar. Li J, Wang Y, Wang Y, Wen X, Ma XN, Chen W, et al. Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates endoplasmic reticulum stress-associated endothelial dysfunction. J Mol Cell Cardiol. Jung TW, Lee SY, Hong HC, Choi HY, Yoo HJ, Baik SH, et al. AMPK activator-mediated inhibition of endoplasmic reticulum stress ameliorates carrageenan-induced insulin resistance through the suppression of selenoprotein P in HepG2 hepatocytes. Mol Cell Endocrinol. Yamamoto E, Kataoka K, Shintaku H, Yamashita T, Tokutomi Y, Dong YF, et al. Novel mechanism and role of angiotensin II induced vascular endothelial injury in hypertensive diastolic heart failure. Davis BJ, Xie Z, Viollet B, Zou MH. Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Tsai CM, Kuo HC, Hsu CN, Huang LT, Tain YL. Metformin reduces asymmetric dimethylarginine and prevents hypertension in spontaneously hypertensive rats. Transl Res. Pitocco D, Zaccardi F, Tarzia P, Milo M, Scavone G, Rizzo P, et al. Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study. Diabetes Obes Metab. Katakam PV, Ujhelyi MR, Hoenig M, Miller AW. Metformin improves vascular function in insulin-resistant rats. Laplante MA, Wu R, Moreau P, de Champlain J. Endothelin mediates superoxide production in angiotensin II-induced hypertension in rats. Free Radic Biol Med. Gumusel B, Tel BC, Demirdamar R, Sahin-Erdemli I. Reactive oxygen species-induced impairment of endothelium-dependent relaxation in rat aortic rings: protection by L-arginine. Eur J Pharmacol. Konior A, Schramm A, Czesnikiewicz-Guzik M, Guzik TJ. NADPH oxidases in vascular pathology. Antioxid Redox Signal. An H, Wei R, Ke J, Yang J, Liu Y, Wang X. Metformin attenuates fluctuating glucose-induced endothelial dysfunction through enhancing GTPCH1-mediated eNOS recoupling and inhibiting NADPH oxidase. J Diabetes Complicat. Piwkowska A, Rogacka D, Jankowski M, Dominiczak MH, Stepiński JK, Angielski S. Metformin induces suppression of NAD P H oxidase activity in podocytes. Download references. Department of Emergency and Critical Care, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. West Coast University, School of Pharmacy, Los Angeles, CA, , USA. California State University, Los Angeles, Los Angeles, CA, , USA. Cardiovascular Division, Department of Medicine, and Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, IA City, IA, , USA. Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, , Korea. You can also search for this author in PubMed Google Scholar. Correspondence to Modar Kassan. The original online version of this article was revised: Due to the presentation of Figure 6B was incorrect. Reprints and permissions. Chen, C. et al. Hypertens Res 42 , — Download citation. Received : 28 September Revised : 23 November Accepted : 20 December Published : 21 January Issue Date : July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Reviews in Endocrine and Metabolic Disorders Skip to main content Thank you for visiting nature. nature hypertension research articles article. Download PDF. This article has been updated. Abstract Metformin is an antidiabetic drug. You have full access to this article via your institution. Empagliflozin maintains capillarization and improves cardiac function in a murine model of left ventricular pressure overload Article Open access 15 September Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway Article Open access 11 November Dapagliflozin attenuates pressure overload-induced myocardial remodeling in mice via activating SIRT1 and inhibiting endoplasmic reticulum stress Article 01 December Introduction Metformin, an oral antidiabetic agent, is usually prescribed as a first-line drug to patients with type-2 diabetes mellitus T2DM by international guidelines [ 1 ]. Materials and methods General protocol in mice All experiments were performed according to the guidelines of Animal Care Committee of Shanghai Jiao Tong University School of Medicine. Western blot analysis Western blot analysis for total and phospho eNOS, phospho PERK, total and phospho eIF2-α, CHOP, GRP78, ATF6, and total and phospho AMPKα dilution, Cell Signaling Technology, Inc, USA was performed in lysates of mesenteric arteries as previously described. Immunofluorescence MRA segments were frozen in Tissue Tek OCT embedding medium Sakura Finetek Europe, The Netherlands. Nicotinamide adenine dinucleotide phosphate NADPH oxidase activity assay Superoxide anion levels generated by NADPH oxidase activity were measured in lysates of aorta and MRA using lucigenin chemiluminescence. Drugs Phenylephrine hydrochloride, acetylcholine, NADPH, angiotensin II, and metformin were obtained from Sigma—Aldrich USA. Results Metformin ameliorated angiotensin II-induced systolic blood pressure We aimed to study the effect of metformin on SBP. Full size image. Discussion In the present study, we demonstrated that metformin inhibited Ang II-induced aberrant ER stress and vascular dysfunction through activation of AMPK. Similar content being viewed by others. References Pernicova I, Korbonits M. Article CAS Google Scholar Giugliano D, De Rosa N, Di Maro G, Marfella R, Acapora R, Buoninconti R, et al. Article CAS Google Scholar He H, Zhao Z, Chen J, Ni y, Zhong J, Yan Z, et al. Article CAS Google Scholar Muntzel MS, Nyeduala B, Barrett S. Article CAS Google Scholar Cody RJ. Article CAS Google Scholar Ohishi M. Article Google Scholar Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Article CAS Google Scholar Campbell DJ. Article CAS Google Scholar Hasty AH, Harrison DG. Article CAS Google Scholar Deji N, Kume S, Araki S, Isshiki K, Araki H, Chin-Kanasaki M, et al. Article CAS Google Scholar Ford RJ, Rush JW. Article CAS Google Scholar Liang B, Wang S, Wang Q, Zhang W, Viollet B, Zhu Y, et al. Article CAS Google Scholar Dong Y, Zhang M, Liang B, Xie Z, Zhao Z, Asfa S, et al. Article CAS Google Scholar Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Article CAS Google Scholar Kassan M, Ait-Aissa K, Radwan E, Mali V, Haddox S, Gabani M, et al. Article CAS Google Scholar Kassan M, Galan M, Partyka M, Trebak M, Matrougui K. Article CAS Google Scholar Linden MA, Lopez KT, Fletcher JA, Morris EM, Meers GM, Siddique S, et al. Article CAS Google Scholar Cai H, Harrison DG. Article CAS Google Scholar Kassan M, Galán M, Partyka M, Saifudeen Z, Henrion D, Trebak M, et al. Article CAS Google Scholar Duan Q, Song P, Ding Y, Zou MH. Article CAS Google Scholar Hamidi Shishavan M, Henning RH, van Buiten A, Goris M, Deelman LE, Buikema H. Article Google Scholar Verma S, Bhanot S, McNeill JH. CAS PubMed Google Scholar Zhou L, Liu H, Wen X, Peng Y, Tian Y, Zhao L. Article CAS Google Scholar Okada K, Minamino T, Tsukamoto Y, Liao Y, Tsukamoto O, Takashima S, et al. Article Google Scholar Cheang WS, Tian XY, Wong WT, Lau CW, Lee SS, Chen ZY, et al. Article CAS Google Scholar Hwang SL, Jeong YT, Li X, Kim YD, Lu Y, Chang YC, et al. Article CAS Google Scholar Kim A, Im M, Ma JY. Article CAS Google Scholar Hu L, Zhou L, Wu X, Liu C, Fan Y, Li Q. PubMed PubMed Central Google Scholar Li J, Wang Y, Wang Y, Wen X, Ma XN, Chen W, et al. Article CAS Google Scholar Jung TW, Lee SY, Hong HC, Choi HY, Yoo HJ, Baik SH, et al. Article CAS Google Scholar Yamamoto E, Kataoka K, Shintaku H, Yamashita T, Tokutomi Y, Dong YF, et al. Part 1: Global Burden of Diabetes. World Health Organization, Geneva, Kannel, D. McGee, Diabetes and cardiovascular disease. The Framingham Study. JAMA , — Article CAS PubMed Google Scholar. Fox, S. Coady, P. Sorlie, R. Pencina, R. Vasan, J. Meigs, D. Levy, P. Savage, Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation 12 , — Article PubMed Google Scholar. Hayward, P. Reaven, W. Wiitala, G. Bahn, D. Reda, L. Ge, M. McCarren, W. Duckworth, N. Emanuele, VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. UK Prospective Diabetes Study Group, Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS BMJ , — Article PubMed Central Google Scholar. Evidence-Based Guideline for the Management of High Blood Pressure in Adults, Report from the panel members appointed to the Eighth Joint National Committee JNC 8. JAMA 5 , — Article CAS Google Scholar. UK Prospective Diabetes Study UKPDS Group, Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes UKPDS Lancet , — Article Google Scholar. Lamanna, M. Monami, E. Mannucci, Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes. Zinman, C. Wanner, J. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O. Johansen, H. Woerle, U. Broedl, S. Inzucchi, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. Madiraju, D. Erion, Y. Rahimi, X. Zhang, D. Braddock, R. Albright, B. Prigaro, J. Wood, S. Bhanot, M. MacDonald, M. Jurczak, J. Camporez, H. Lee, G. Cline, V. Samuel, R. Kibbey, G. Shulman, Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature , — Article CAS PubMed PubMed Central Google Scholar. Kosegawa, S. Katayama, C. Kikuchi, H. Kashiwabara, K. Negishi, J. Ishii, Y. Oka, Metformin decreases blood pressure and obesity in OLETF rats via improvement of insulin resistance. Bhalla, K. Toth, E. Tan, R. Bhatty, E. Mathias, R. Sharma, Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat. Muntzel, I. Hamidou, S. Barrett, Metformin attenuates salt-induced hypertension in spontaneously hypertensive rats. Hypertension 33 , — Muntzel, A. Abe, J. Petersen, Effects of adrenergic, cholinergic and ganglionic blockade on acute depressor responses to metformin in spontaneously hypertensive rats. CAS PubMed Google Scholar. Kirpichnikov, S. McFarlane, J. Sowers, Metformin: an update. Nagi, J. Yudkin, Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care 16 , — Chan, B. Tomlinson, Critchley JAJH, C. Cockram, R. Walden, Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. Giugliano, N. De Rosa, G. Di Maro, R. Marfella, R. Acampora, R. Buoniconti, F. Landin, L. Tengborn, U. Smith, Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. Giugliano, A. Quatraro, G. Consoli, A. Minei, A. Ceriello, N. De Rosa, F. Campbell, C. Duncan, N. Patton, T. Broadhead, G. Tucker, H. Woods, The effect of metformin on Glycaemic control, intermediary metabolism and blood pressure in non-insulin-dependent diabetes mellitus. Gudbjörnsdottir, P. Friberg, M. Elam, S. Attvall, P. Lönnroth, G. Wallin, The effect of metformin and insulin on sympathetic nerve activity, norepinephrine spillover and blood pressure in obese, insulin resistant, normoglycemic, hypertensive men. Blood Press. Mourão Júnior, J. Sá, O. Guedes, S. Dib, Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin. Kooy, J. Jager, P. Lehert, D. Bets, M. Wulffele, A. Donker, C. Stehouwer, Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Snorgaard, L. Kober, J. Carlsen, The effect of metformin on blood pressure and metabolism in nondiabetic hypertensive patients. Friedewald, R. Levy, D. Fredrickson, Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Alberti, P. Zimmet, J. Shaw, Metabolic syndrome-a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Malachias, R. Franco, C. Forjaz, A. Pierin, M. Gowdak, M. Klein, V. VI Diretrizes Brasileiras de Hipertensão. Riegel, L. Moreira, S. Fuchs, M. Gus, G. Nunes, V. Correa Jr, M. Wiehe, C. Gonçalves, F. Fernandes, F. Fuchs, Long-term effectiveness of non-drug recommendations to treat hypertension in a clinical setting. Wulffelé, A. Kooy, D. De Zeeuw, C. Stehouwer, R. Gansevoort, The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. Zhou, H. Liu, X. Wen, Y. |
| Helpful Links | In the original trial pressurf total Metformin and blood pressure pgessure in the metformin group and patients in the placebo group Metfrmin the Safe natural weight loss and had usable outcome measures at baseline and follow-up. Endothelium-dependent contractions in SHR: a tale of prostanoid TP and IP receptors. Find a doctor. Barrett, Metformin attenuates salt-induced hypertension in spontaneously hypertensive rats. About this article. Pharmacol Rep 65— |
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