Rossi N F, O'Leary D S, Woodbury D, Chen H
Department of Medicine, Wayne State University School of Medicine, and John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan 48201, USA.
Am J Physiol Endocrinol Metab. 2000 Jul;279(1):E18-24. doi: 10.1152/ajpendo.2000.279.1.E18.
This study sought to identify whether central endothelin (ET) receptor activation contributes to the elevated pressure in spontaneously hypertensive rats (SHR) and whether an ET-stimulated vasopressin (AVP) release mediates the increased pressure. In Wistar Kyoto (WKY) rats, intracerebroventricular ET-1 induced a dose-dependent pressor response that was shifted rightward in SHR. ET(A) antagonism decreased mean arterial pressure in baroreflex-intact SHR (P<0.01), consistent with inhibition of endogenous ET-1, and blocked the pressor response to exogenous ET-1 in both strains. ET-1 increased AVP only after sinoaortic denervation (P<0.05). Contrary to WKY, sinoaortic denervation was required to elicit a significant pressor response with 5 pmol ET-1 in SHR. Sinoaortic denervation permitted ET-1 to increase AVP in both strains, and peripheral V(1) blockade decreased pressure in denervated but not intact rats. After nitroprusside normalized pressure in SHR, the pressor and AVP secretory responses paralleled those in WKY. Thus endogenous ET(A) receptor mechanisms contribute to hypertension, independent of AVP, in baroreflex-intact SHR. Although blunted in the hypertensive state, the arterial baroreflex buffers the ET-1-induced pressor and AVP secretory responses in both strains.
本研究旨在确定中枢内皮素（ET）受体激活是否导致自发性高血压大鼠（SHR）血压升高，以及ET刺激的血管加压素（AVP）释放是否介导血压升高。在Wistar Kyoto（WKY）大鼠中，脑室内注射ET-1可诱导剂量依赖性的升压反应，该反应在SHR中向右移位。ET（A）拮抗剂可降低压力感受性反射完整的SHR的平均动脉压（P<0.01），这与内源性ET-1的抑制作用一致，并阻断了两种品系对外源性ET-1的升压反应。仅在去窦主动脉神经后，ET-1才增加AVP（P<0.05）。与WKY相反，在SHR中，需要去窦主动脉神经才能用5 pmol ET-1引发明显的升压反应。去窦主动脉神经使ET-1在两种品系中均能增加AVP，外周V（1）受体阻断可降低去神经大鼠而非完整大鼠的血压。在用硝普钠使SHR血压正常化后，升压反应和AVP分泌反应与WKY中的反应相似。因此，在压力感受性反射完整的SHR中，内源性ET（A）受体机制独立于AVP而导致高血压。尽管在高血压状态下减弱，但动脉压力感受性反射可缓冲两种品系中ET-1诱导的升压反应和AVP分泌反应。
