Long-term social stress induces nitric oxide-independent endothelial dysfunction in normotensive rats

Abstract

As chronic stress is a significant risk factor for several cardiovascular disorders, this study investigated the hypothesis that long-term stress produced by crowding may lead to alterations in nitric oxide (NO) production and NO-dependent relaxation in the course of stress, resulting in endothelial dysfunction and hypertension in Wistar-Kyoto (WKY) rats. For this purpose, male WKY rats were divided into control (480 cm2/rat, four rats/cage, n = 8) and crowded (200 cm2/rat, five rats/cage, n = 10) groups for 8 or 12 weeks. Vasorelaxation was evaluated in vitro as a response to acetylcholine (ACh) of femoral arteries pre-contracted by serotonin, before and after NO synthase inhibition (N (G)-nitro-l-arginine methyl ester, 300 μmol/l). Crowding increased plasma corticosterone concentration but failed to affect blood pressure (determined by tail-cuff plethysmography) of rats. NO production was unchanged in the hypothalamus and left ventricle of both stressed groups; however it was significantly elevated in the aorta. Maximal ACh-induced relaxation was elevated significantly after 8-week stress, but reduced after 12 weeks. Stress elevated the NO-dependent component and reduced the NO-independent component of ACh-induced relaxation in both crowded groups. However, a reduction in the NO-independent component was more pronounced after 12-week versus 8-week stress. In conclusion, elevated endothelium-dependent relaxation was observed after 8-week stress, while the extension of stress exposure resulted in a reduction in arterial relaxation associated with a more pronounced decrease of its NO-independent component. Thus, elevation of the NO-dependent component of relaxation can be considered as an adaptation mechanism, and impairment of NO-independent relaxation might be the initial step in chronic stress-induced cardiovascular disorders.

Effect of noise stress on cardiovascular system in adult male albino rat: implication of stress hormones, endothelial dysfunction and oxidative stress

“…NO is accepted as oxygen free radical that has harmful effects on cardiovascular system (Demirel et al 2009). This finding is in agreement with the study of Puzserova et al who postulated that long-term exposure to chronic social stress reduced the NO-independent relaxation in normotensive rats that might be the initial step in chronic stress-induced cardiovascular disorders (Puzserova et al 2013). In contrast to our finding, other researchers postulated that the level of NO in erythrocytes of workers in noisy workplaces is lower than the workers in non-noisy places and this could be an adaptive mechanism to chronic exposure to loud noise (Pinar et al 2011).…”

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

“…Heart rate (HR) and systolic BP were determined by tail-cuff method between 08.00 and 11.00, as described in detail previously (Puzserova et al, 2013b). Each BP and HR value was calculated as the average of five measurements.…”

“…Plasma samples were then stored at -80°C until analysis. Plasma corticosterone (pCort) was measured in duplicate in 20 μl of plasma by an enzyme immunoassay kit (Arbor Assays, Ann Arbor, MI, United States), as described in detail previously (Puzserova et al, 2013b). …”

“…Activity of NO synthase (NOS) was determined by conversion of [ 3 H]- L -arginine (MP Biomedicals, Santa Ana, CA, United States) in 20% crude tissue homogenates of the LHV, aorta, hypothalamus and brainstem, as described previously (Puzserova et al, 2013b), and was expressed as pmol/min/mg of protein.…”

“…Normalization, including calculations for normalized inner diameter, was performed as described by Puzserova et al (2013b). The experimental protocol consisted of the following steps: (a) Modified physiological salt solution (PSS, 118.99 mmol/l NaCl, 4.69 mmol/l KCl, 25 mmol/l NaHCO 3 , 1.17 mmol/l MgSO 4 .7H 2 O, 1.18 mmol/l KH 2 PO 4 , 2.5 mmol/l CaCl 2 .2H 2 O, 0.03 mmol/l Na 2 EDTA, 5.5 mmol/l glucose) in the myograph chamber was changed to depolarizing solution KPSS (i.e., PSS in which NaCl was replaced with KCl with concentration of K + 125 mmol/l) for 2 min and contraction was measured.…”