Endothelin-1 in hypertension in the baroreflex-intact SHR: a role independent from vasopressin release.
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.
Rossi
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NF
Department of Medicine, Wayne State University School of Medicine, and John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan 48201, USA.
O'Leary
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DS
Woodbury
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D
Chen
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H
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D019332:Endothelin-1 / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D017483:Receptors, Vasopressin / Q000378:metabolism; D012850:Sinus of Valsalva / Q000294:innervation
D019332:Endothelin-1; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin