Enhanced renal vascular responsiveness to angiotensin ii in hypertensive ren-2 transgenic rats. Jacinto, Severina M., John J. Mullins, and Kenneth D. Mitchell. 1Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112; and 2Centre for Genome Research, University of Edinburgh, Edinburgh, EH9 3JQ, Scotland
APStracts 5:0201F, 1998.
The present study was performed to evaluate the renal vascular responsiveness to angiotensin II (ANG II) in hypertensive transgenic rats [TGR; strain name: TGR(mRen2)27] harboring the mouse Ren-2 renin gene. Renal blood flow responses to either intravenous or intrarenal arterial administration of ANG II were assessed in pentobarbital -anesthetized female heterozygous TGR (9-12 wk-old) and age-matched transgene-negative Hannover Sprague Dawley rats (HanSD). Intravenous bolus injections of 15 and 30 ng of ANG II elicited dose-dependent increases in mean arterial blood pressure and decreases in renal blood flow in both TGR and HanSD. However, the magnitude of the increases in arterial blood pressure was greater in TGR than in HanSD (24+/-1 vs. 17+/-2 mmHg and 33+/-2 vs. 25+/-1 mmHg, respectively, P<0.05 in both cases). Similarly, the magnitude of the decrease in renal blood flow elicited by intravenous administration of 15 ng of ANG II was greater in TGR than HanSD (-62+/-3 vs. -52+/-5%, P<0.05). Intrarenal arterial administration of 1.5 and 3 ng of ANG II did not alter mean arterial pressure in either group but elicited larger decreases in renal blood flow in TGR than in HanSD (-24+/-2 vs. -13+/-1% and -41+/-5 vs. -30+/-2%, respectively, P<0.05 in both cases). In contrast, intrarenal arterial administration of norepinephrine (40 and 80 ng) elicited smaller decreases in renal blood flow in TGR than in HanSD (-24+/-3 vs. -40+/-6% and -51+/-9 vs. -71+/-8%, respectively, P<0.05 in both cases) indicating that TGR do not exhibit a generalized increase in renal vascular responsiveness to endogenous vasoconstrictors. Further, the enhanced renal vascular responsiveness to ANG II does not appear to reflect an impaired renal vascular responsiveness to endogenous vasodilator factors since intrarenal administration of bradykinin and acetylcholine elicited larger increases in renal blood flow in TGR than in HanSD. The present findings indicate that hypertensive TGR exhibit exaggerated renal and peripheral vascular responses to ANG II, which likely contributes to an increased renal and peripheral vascular resistance and thereby to the hypertension in TGR. 

Received 13 July 1998; accepted in final form 5 November 1998.
APS Manuscript Number F167-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 20 November 1998