Bjørnstad-Ostensen A, Holte H R, Berg T
Department of Physiology, University of Oslo, Norway.
Hypertension. 1997 Jan;29(1 Pt 1):53-7. doi: 10.1161/01.hyp.29.1.53.
We studied the role of nitric oxide and adrenergic activation in the blood pressure (BP) response to exogenous bradykinin in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Rats were pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the alpha-adrenergic receptor antagonist phentolamine together with L-NAME, or phentolamine alone. Sham-injected rats were used as controls. All rats subsequently received bradykinin (3, 6, and 30 micrograms/kg i.v.). Bradykinin induced a concentration-dependent fall in BP in both WKY and SHR (P < .0005). The change in BP was greater in SHR than WKY (P < .0001). BP before bradykinin administration was elevated in the L-NAME group in both strains. In WKY, L-NAME or L-NAME plus phentolamine did not alter the delta BP concentration-response curve to bradykinin (P = NS), whereas in SHR, the delta BP concentration-response curve was attenuated (P < .0048). The attenuation was observed for the two lower bradykinin doses (P < .0005) but not the highest. In SHR, phentolamine alone reduced BP before bradykinin to the same level as in WKY controls, and its delta BP concentration-response curve was not different from that of the normotensive controls or L-NAME and L-NAME plus phentolamine SHR groups. No difference was observed in the duration of the hypotensive response in SHR compared with WKY. The present results confirm that in normotensive rats, the hypotensive effect of bradykinin was mediated by an unknown mechanism other than through the release of nitric oxide. However, in SHR, this mechanism was amplified by additional activation of nitric oxide synthesis. This bradykinin-activated nitric oxide production may be a pressure-induced mechanism to counteract the hypertensive condition.
我们研究了一氧化氮和肾上腺素能激活在自发性高血压大鼠（SHR）与正常血压的Wistar-Kyoto大鼠（WKY）对外源性缓激肽的血压（BP）反应中的作用。大鼠分别用一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）、α-肾上腺素能受体拮抗剂酚妥拉明与L-NAME联合处理或仅用酚妥拉明预处理。假注射大鼠用作对照。随后所有大鼠静脉注射缓激肽（3、6和30微克/千克）。缓激肽在WKY和SHR中均引起血压浓度依赖性下降（P <.0005）。SHR中的血压变化大于WKY（P <.0001）。两种品系的L-NAME组在给予缓激肽前血压均升高。在WKY中，L-NAME或L-NAME加酚妥拉明未改变对缓激肽的ΔBP浓度-反应曲线（P =无显著性差异），而在SHR中，ΔBP浓度-反应曲线减弱（P <.0048）。在较低的两个缓激肽剂量下观察到这种减弱（P <.0005），但最高剂量时未观察到。在SHR中，单独使用酚妥拉明可使给予缓激肽前的血压降至与WKY对照组相同水平，其ΔBP浓度-反应曲线与正常血压对照组或L-NAME以及L-NAME加酚妥拉明的SHR组无差异。与WKY相比，SHR中降压反应的持续时间未观察到差异。目前的结果证实，在正常血压大鼠中，缓激肽的降压作用是通过一氧化氮释放以外的未知机制介导的。然而，在SHR中，这种机制通过一氧化氮合成的额外激活而增强。这种缓激肽激活的一氧化氮产生可能是一种压力诱导机制，以对抗高血压状态。
