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(Hypertension. 2001;38:353.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Enhanced Interaction Between Renovascular ₂-Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

Edwin K. Jackson; William A. Herzer; Curtis K. Kost, Jr; Subhash J. Vyas

Center for Clinical Pharmacology, Departments of Pharmacology (E.K.J., C.K.K.) and Medicine (E.K.J., W.A.H., C.K.K., S.J.V.), University of Pittsburgh Medical Center, Pa.

Correspondence to Edwin K. Jackson, PhD, Center for Clinical Pharmacology, Department of Medicine, 623 Scaife Hall, 3550 Terrace St, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. E-mail edj+{at}pitt.edu

Abstract—— In spontaneously hypertensive rats (SHR), hypertension is mediated in part by an enhanced renovascular response to angiotensin (Ang) II. Pertussis toxin normalizes renovascular responses to Ang II and lowers blood pressure in SHR, suggesting a role for altered G_i signaling in the enhanced renovascular response to Ang II in SHR. To further investigate this hypothesis, we measured reductions in renal blood flow and increases in renovascular resistance in response to intrarenal infusions of Ang II in the presence and absence of coactivation of ₂-adrenoceptors (ie, receptors selectively coupled to G_i) with UK 14,304 in adrenalectomized, renal-denervated, captopril-pretreated SHR and normotensive Wistar-Kyoto rats. In SHR, but not Wistar-Kyoto rats, UK 14,304 markedly enhanced renovascular responses to Ang II and vasopressin. However, UK 14,304 did not enhance renovascular responses to methoxamine (₁-adrenoceptor agonist) in either strain. In uninephrectomized, normotensive Sprague-Dawley animals and in Sprague-Dawley rats with nongenetic hypertension induced by uninephrectomy, chronic administration of deoxycorticosterone acetate, and 1% saline as drinking water, UK 14,304 had little or no effect on renovascular responses to Ang II. In SHR, intrarenal infusions of U73122, a phospholipase C/D inhibitor, blocked the enhancement of renovascular responses to Ang II by UK 14,304. We conclude that activation of ₂-adrenoceptors selectively enhances renovascular responses to Ang II and vasopressin in vivo in animals with genetic hypertensive but not in normotensive animals or animals with acquired hypertension. These results suggest that in SHR, there is a genetically mediated enhanced cross talk between the G_i signal transduction pathway and signal transduction pathways activated by Ang II and vasopressin, but not methoxamine, and involving phospholipase C and/or D.

Key Words: hypertension, genetic • angiotensin II • vasopressin • kidney • G protein • receptors, adrenergic, alpha

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