Vascular and hemodynamic effects of behavioral stress in borderline hypertensive and Wistar-Kyoto rats

Abstract

In borderline hypertensive rats (BHR), behavioral stress produces hypertension, which has been attributed to increases in sympathetic nervous system activity and peripheral changes in vascular structure. However, the mechanisms mediating development of stress-induced hypertension have not been well defined. Experiments were designed to determine hemodynamic effects and changes in small mesenteric artery (≈300 μm) vascular reactivity in response to 10 days of air-jet stress (2 h/day) in BHR and in Wistar-Kyoto (WKY) rats. The acute stress-induced increase in mean arterial pressure (AP) was impaired in WKY rats compared with BHR on day 1, and habituation developed to the increase in AP in BHR, but not WKY rats. Conversely, WKY rats adapted to the stress-induced tachycardia to a larger extent than BHR. The mechanisms mediating endothelium-dependent relaxation to acetylcholine (ACh) were altered in small mesenteric arteries isolated from WKY rats and BHR after 10 days of air-jet stress. Inhibition of nitric oxide synthase activity had a significantly larger inhibitory effect on ACh-induced relaxation in vessels from stressed compared with control BHR. Also, cyclooxygenase products contributed to ACh-induced relaxation of small mesenteric arteries from stressed WKY rats, but not control WKY rats. Endothelium-independent relaxation to nitroprusside was impaired in vessels from stressed WKY rats, but not stressed BHR. Finally, contraction to phenylephrine was impaired in vessels from stressed BHR, but not WKY rats. In conclusion, changes in vascular reactivity induced by air-jet stress appear to correlate with, and may contribute to, the differential hemodynamic adaptations to stress observed in WKY rats and BHR.

Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation

“…Prolonged exposure to stress ultimately results in elevated blood pressure that persists even after removal of the stress (29). Although 10 days of air-jet stress as used in this study does not alter the resting arterial blood pressure, changes in vascular reactivity can be detected in this period of time before the development of hypertension (10,11). Therefore, 10-day exposure of BHRs to stress offers a good model to study changes in vascular function and structure before the development of hypertension allowing for determination of vascular changes independent of changes in blood pressure.…”

“…Second, high-salt diet causes the development of hypertension (3). Third, exposure to stress for 10 days alters vascular contraction and relaxation in BHRs (11,13). Enhanced sympathetic nervous system activity and peripheral vascular structural changes leading to increased vascular resistance are believed to contribute to stress-induced hypertension.…”

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

“…SHR exhibit exaggerated cardiovascular responses to acute stress and develop glucocorticoiddependent hypertension (20,41,50). BHR also have enhanced stress reactivity and are susceptible to stress-induced hypertension (21,51). Thus, we hypothesized that endogenous glucocorticoids would exert a greater influence on stress responsiveness in BHR relative to WKY rats.…”

Experimental Models Used in Hypertension Research

“…Akut çevresel strese maruziyet sırasında, bu sıçan soyunda plazma noradrenalin derişiminin arttığı ve vasküler reaktivitede değişiklikler gözlendiği bildirilmiştir (79). BHR'ler yüksek plazma vazopressin derişimi ve kardiyak hipertrofi gelişmesine de duyarlıdır (60).…”