Institute of Normal and Pathological Physiology, Centre of Excellence for Examination of Regulatory Role of Nitric Oxide in Civilisation Diseases, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Stress. 2013 May;16(3):331-9. doi: 10.3109/10253890.2012.725116. Epub 2012 Oct 1.
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.
由于慢性应激是几种心血管疾病的重要危险因素，因此本研究假设，拥挤引起的长期应激可能导致在应激过程中一氧化氮（NO）产生和 NO 依赖性松弛的改变，从而导致 Wistar-Kyoto（WKY）大鼠的内皮功能障碍和高血压。为此，将雄性 WKY 大鼠分为对照组（480 cm2/大鼠，4 只/笼，n = 8）和拥挤组（200 cm2/大鼠，5 只/笼，n = 10），分别饲养 8 或 12 周。通过预先用 5-羟色胺收缩的股动脉对乙酰胆碱（ACh）的血管舒张反应来评估体外血管舒张，然后抑制一氧化氮合酶（N（G）-硝基-L-精氨酸甲酯，300 μmol/l）。拥挤增加了血浆皮质酮浓度，但对大鼠的血压（通过尾套容积描记法测定）没有影响。在应激的下丘脑和左心室中，NO 产生没有变化；然而，在主动脉中却显著增加。8 周应激后，最大 ACh 诱导的松弛显著升高，但 12 周后降低。应激增加了拥挤组的 ACh 诱导松弛的 NO 依赖性成分和降低了其非依赖性成分。然而，12 周应激后非依赖性成分的减少比 8 周应激后更为明显。总之，在 8 周应激后观察到内皮依赖性松弛增加，而延长应激暴露导致动脉松弛减少，与非依赖性成分减少更为明显。因此，可以认为升高的松弛的 NO 依赖性成分是一种适应机制，而 NO 非依赖性松弛的损害可能是慢性应激引起的心血管疾病的初始步骤。
