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

Abstract

This study was designed to investigate whether oxidative stress, nitric oxide (NO) deficiency and/or endothelial dysfunction (ED) are present in young borderline hypertensive rats (BHR) and whether these pathologies can be causally involved in the initiation of blood pressure (BP) increases. Additionally, we tested the hypothesis that crowding stress, experienced during the peripubertal period, may produce persistent or delayed disorders in corticosterone release, NO synthesis, oxidative status and/or endothelial function that could accelerate BP increases. To test these hypotheses, 5-week-old male BHR and normotensive Wistar-Kyoto rats (WKY) were either kept in control conditions (for 2 and 4 weeks, respectively) or exposed to social stress produced by crowding for 2 weeks (stress). After cessation of crowding, a group of rats of each phenotype was kept in control conditions for the next 2 weeks (post-stress). Systolic BP of 5-week-old BHR was significantly increased vs. age-matched WKY (127 ± 3 vs. 104 ± 3 mmHg, p < 0.01) and remained significantly higher throughout the course of the experiment. Despite elevated BP, no signs of oxidative damage to plasma lipids, NO deficiency or ED were observed in control BHR vs. age-matched WKY. Crowding stress elevated plasma corticosterone and accelerated BP increases only in BHR; these effects persisted 2 weeks post-stress. Crowding failed to induce oxidative damage to plasma lipids in either phenotype, but it produced persistent decreases in NO production in the hypothalamus and brainstem of both strains of rats, as well as in the hearts of BHR. In contrast, crowding failed to reduce NO production in the aortae or acetylcholine-induced relaxations of the femoral arteries in both strains investigated. However, significantly reduced aortic NO production was observed in BHR 2 weeks post-stress vs. age-matched controls, which was in agreement with reduced NO-dependent components of vasorelaxation. In conclusion, this study’s data showed that oxidative stress, NO deficiency and ED are not causally involved in initiation of blood pressure increase in BHR. However, exposure to stressful environments produced persistent increases in plasma corticosterone and reductions of brain and cardiac NO production followed by a delayed decrease in the NO-dependent component of endothelium-dependent relaxation—changes that collectively accelerated BP increases only in BHR.

Short- and Long-Term Repeated Forced Swim Stress Induce Depressive-Like Phenotype in Mice: Effectiveness of 3-[(4-Chlorophenyl)Selanyl]-1-Methyl-1H-Indole

“…These findings, together with the significant positive correlation with behavioral tests, show the ability of CMI to modulate hyperactivity of the HPA axis, an effect that can play a role in its antidepressant properties. The alterations in the HPA axis are caused especially when there is exposure to acute stress (Browne et al, 2014), but some authors demonstrated the alteration in the corticosterone levels caused by long-term stress (Dallman et al, 2004;Bernatova et al, 2018). In addition, HPA axis activation can produce damaging physiological effects and exert a profound impact on brain function (McEwen, 2000;Tsigos and Chrousos, 2002).…”

“…The alterations in the HPA axis are caused especially when there is exposure to acute stress (Browne et al, 2014 ), but some authors demonstrated the alteration in the corticosterone levels caused by long-term stress (Dallman et al, 2004 ; Bernatova et al, 2018 ). In addition, HPA axis activation can produce damaging physiological effects and exert a profound impact on brain function (McEwen, 2000 ; Tsigos and Chrousos, 2002 ).…”

The Effect of Swimming on Anxiety-Like Behaviors and Corticosterone in Stressed and Unstressed Rats

“…[2][3][4][5][6] Elevated plasma cortisol levels are common in patients with anxiety [40]. In CMS models, the persistency of elevated plasma corticosterone levels has been demonstrated after stress withdrawal [41,42]. Elevated corticosterone in CS + ST, which was similar to the CS condition, can be justified by persistency of the effect of the two stressors, CMS and swimming training, on corticosterone, which continued for a relatively long time (eight weeks).…”

Splenic Blood Flow Increases after Hypothermic Stimulus (Cold Pressor Test): A Perfusion Magnetic Resonance Study

“…Systemic disorders affecting the endothelial function, such as those seen in smokers [10], in patients with early atherosclerosis [33], or in patients with diabetes [12], alter these mechanisms and hamper the production of NO, resulting in an impairment of vasodilation response [34–36].…”