For example, exposure to dexamethasone, which is a synthetic glucocorticoid, reduced eNOS expression in the endothelial cell cultures Wallerath et al. Simmons et al.

In addition, in the isolated mesenteric arteries, dexamethasone reduced nNOS-mediated NO release in the arteries from spontaneously hypertensive but not normotensive rats Aras-López et al. Recently, Lee et al. These studies suggest diverse effects of chronic glucocorticoid overload on vascular NO production, which may differ in normotensive and pre hypertensive subjects.

As this study was not primarily focused on the role of individual NOSs in stress-induced responses, the contributions of individual NOSs in crowding stress-induced NO-dependent vascular changes in the conduit arteries remains to be elucidated.

We showed that the impairment of overall endothelial function does not contribute to the maintenance of high BP in young, post-stress BHR, despite altered mechanism s mediating endothelium-dependent relaxations.

Thus, this mechanism may provide a link between the delayed effects of chronic stress and other stress-induced disorders such as atherosclerosis or insulin resistance Kawashima and Yokoyama, ; Kim et al. Consistent with the unchanged vasorelaxations, no alterations in oxidative status were observed in stressed rats in this study.

However, SOD activities in post-stressed BHR were significantly reduced compared to those in post-stressed WKY. This might be involved in slow progress of oxidative damage to plasma LP in BHR, consistent with the positive correlation between total antioxidant capacity of plasma and LP.

A similar correlation was observed previously in rats with various genetic predispositions to hypertension Horvathova et al. In addition, the lack of oxidative damage to lipids in blood does not exclude local tissue oxidative stress. Specifically, oxidative stress in the brain can contribute to hypertension development via increased sympathoexcitation Kishi and Hirooka, We found that crowding led to significant increases in pCort and an acceleration of BP rise only in BHR.

Similarly, higher pressor responses to various stressors have been shown previously in adult BHR males compared with WKY Fuchs et al. Because crowding stress failed to induce oxidative stress and ED, the differences in crowding-induced BP increases might be related to the central effects of corticosterone.

Bechtold et al. In this study, crowding stress elevated BP and pCort while reducing NO production in the hypothalamus and brainstem in BHR. NO is an important mediator in regulation of the HPA axis under both rest and stress, that is involved in HPA axis attenuation and activation, respectively for review see Puzserova and Bernatova, Regarding delayed effect of stress, in our study all BP, pCort and NO production in the selected brain areas failed to recover 2 weeks post-stress.

Persistent increases of pCort after stress may result from epigenetic mechanisms such as DNA methylation of glucocorticoid receptors Turecki and Meaney, , which may impede the HPA axis negative feedback regulation.

Subsequently, chronic high glucocorticoid levels may decrease NO bioavailability in various brain areas. It has been shown that high levels of glucocorticoids led to alterations in neuronal NO release in the central nervous system, which is an important mechanism in development of hypertension Goodwin and Geller, Thus, the interaction of stress-induced NO insufficiency in the vascular and central nervous system with accentuated noradrenergic function and sympathetic nervous system SNS excitation may provoke BP increases in BHR, similar to those in unstressed SHR.

In SHR, altered noradrenergic function and increased SNS tone can be considered to be mechanisms underlying hypertension Hojna et al. This study yields several important results. First, we found that generalized oxidative stress, vascular NO deficiency and ED are not causally involved in the initiation of BP increases in BHR, as these pathologies were not present in 7-week or 9-week control BHR despite significantly elevated BP vs.

young normotensive rats. Second, we observed that exposure to stressful environments reduced NO production in the hypothalamus and brainstem of WKY without increasing BP.

In contrast, the same environments in BHR resulted in persistent increases in pCort, reductions in brain and cardiac NO production, and delayed alterations in endothelial function that worked together to accelerate the increase of BP in BHR.

Thus, relatively short-term, mild social stress, experienced in early life, can create persistent impairment in HPA axis regulation followed by accelerations of BP increase in the offspring of hypertensive mothers and normotensive fathers.

IB designed the research studies, conducted selected experiments, performed statistical analysis, and wrote the manuscript. AP and IZ participated in statistical analysis and writing of the manuscript.

AP, PB, NS, MH, and ZK carried out the studies and analyzed the data. IB had primary responsibility for the final content. All authors read and approved the final manuscript. This study was supported by grants from the Slovak Research and Development Agency No.

APVV and the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and the Slovak Academy of Sciences Nos. PB was supported by the Schwarz Fund of the Slovak Academy of Sciences. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The authors thank Mrs. Petova and P. Slezak, Ph. for providing technical assistance. They also thank Dr. Josef Zicha, Ph. for critical reading of the manuscript. Alastalo, H. Early life stress and blood pressure levels in late adulthood. doi: PubMed Abstract CrossRef Full Text Google Scholar.

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Keywords : crowding stress, borderline hypertension, oxidative stress, corticosterone, nitric oxide, endothelial dysfunction. Citation: Bernatova I, Puzserova A, Balis P, Sestakova N, Horvathova M, Kralovicova Z and Zitnanova I Chronic Stress Produces Persistent Increases in Plasma Corticosterone, Reductions in Brain and Cardiac Nitric Oxide Production, and Delayed Alterations in Endothelial Function in Young Prehypertensive Rats.

Received: 01 December ; Accepted: 06 August ; Published: 29 August Copyright © Bernatova, Puzserova, Balis, Sestakova, Horvathova, Kralovicova and Zitnanova.

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ORIGINAL RESEARCH article Front. This article is part of the Research Topic Oxidative Stress Revisited - Major Role in Vascular Diseases View all 13 articles.

Chronic Stress Produces Persistent Increases in Plasma Corticosterone, Reductions in Brain and Cardiac Nitric Oxide Production, and Delayed Alterations in Endothelial Function in Young Prehypertensive Rats. They get secreted from a nerve cell and then travel to another nerve cell where it drops the instructions and thus influences the occurrence of specific chemical reactions.

They play an important role in management of varied bodily functions such as emotional response, motion, and physical capacity to feel pain and pleasure.

In the general populous, dopamine, serotonin, and norepinephrine are the most well- known neurotransmitters. Nitric oxide NO is a gas that can also act as a chemical messenger in the brain. It is produced in every organ and tissue of the body. NO is created by L-arginine essential amino acid via catalytic action of NO synthase NOS enzyme.

Recent research work has shown that the nitric oxide neurotransmitter can help regulate anxiety, social behaviors, and other emotional and psychological aspects.

This neurotransmitter is labile and has less than five seconds half-life at body temperature. Hence, most studies indirectly manipulate the neurotransmitter by affecting its NOS synthetic enzyme. Anxiety not only adversely affects the emotional side but also results in physical abnormalities.

Hence it is important to manage anxiety. Many studies have shown the co-relation between anxiety and nitric oxide levels. Additionally, the neurotransmitter is also important to sexual and cardiac health and living a long, healthy life.

This neurotransmitter gets produced by the blood vessels lining called endothelium. Some of the common causes and risk factors that may trigger fluctuation in nitric oxide levels are as follows:.

Quitting smoking, exercising, intake of nitric oxide supplements, and eating a balanced healthy diet with green leafy veggies, etc. can help increase NO levels. Your email address will not be published. Thanks for your article.

Beetroot concentrate with high levels of nitrate is being extensively researched and utilised with athletes and in food supplements to stimulate the release of nitric oxide in the body check beet — it from UK if interested — highly recommended.