INCREASED PRESSOR FUNCTION OF CENTRAL VASOPRESSINERGIC SYSTEM IN HYPERTENSIVE RENIN TRANSGENIC RATS

Objective Renin transgenic hypertensive rats [TGR(mRen2)27] have incre ased contents of angiotensin II and arginine vasopressin (AVP) in the cardiovascular brain regions. The aim of the present study was to eval uate the effects of centrally released AVP on the regulation of baseli ne blood pressure in TGR(mRen2)27 rats and to determine the interactio n between AVP and angiotensin II in the central control of blood press ure in this model of hypertension. Design Three basic series of experi ments were performed on 20 TGR(mRen2)27 and 20 Hannover Sprague-Dawley conscious rats, chronically instrumented with lateral cerebral ventri cle (LCV) cannulae and femoral artery catheters. In series 1, blood pr essure and heart rate were recorded during an LCV infusion of artifici al cerebrospinal fluid before and after LCV administration of angioten sin II. In series 2, the effects of an LCV administration of angiotens in II (100 ng) on mean arterial pressure and the heart rate were deter mined during LCV infusion of a selective AVP receptor (V-1) antagonist {1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine vasopressin (MeCAAVP) and d(CH2)(5)[Tyr(Me)(2),Ala-NH29]AVP} or a selective angio tensin II type 1 (AT(1)) receptor antagonist (losartan) or both. In se ries 3, mean arterial pressure and the heart rate were determined afte r an LCV injection of either AVP (10 ng) or AVP together with angioten sin II. Results The LCV infusions of antagonists to V-1 and AT(1) rece ptors caused significant comparable decreases in baseline MAP in TGR(m Ren2)27 but not in Sprague-Dawley rats. Angiotensin II elicited signif icant presser responses, both in TGR(mRen2)27 and in Sprague-Dawley ra ts. Blockade of V-1 receptors significantly reduced the duration and t he maximum amplitude of the central presser response to angiotensin II in TGR(mRen2)27 rats, whereas in Sprague-Dawley rats the maximum pres ser effect was not significantly altered. In both strains, the presser response to angiotensin II was abolished by blockade of AT(1) recepto rs, Conclusions The results indicate that the elevated blood pressure in TGR(mRen2)27 rats is partly caused by increased function of the bra in angiotensinergic AT(1) and vasopressinergic V-1 systems. Centrally released AVP is involved in mediation of the presser effect exerted by centrally applied angiotensin II in TGR(mRen2)27 rats. (C) 1998 Lippi ncott Williams & Wilkins.