Angiotensin II-Induced renal vasoconstriction in genetic hypertension

Previous studies demonstrate that renovascular responses to angiotensin II (Ang II) are enhanced in spontaneously hypertensive rats (SHRs); however, i t is possible that this hyperresponsiveness is mediated by Ang II-induced r elease of substances from the adrenal gland. Previous studies also show tha t pertussis toxin normalizes renovascular responses to Ang II in SHRs; howe ver, it is possible that this response is mediated by effects of pertussis toxin on endogenous Ang II levels and/or the sympathoadrenal axis. The purp ose of this study was 2-fold: 1) to determine whether the renovascular resp onse to Ang II in SHRs is enhanced even in adrenalectomized SHRs and 2) to determine whether pertussis toxin normalizes enhanced renovascular response s to Ang II when pertussis toxin-induced changes in the renin-angiotensin s ystem and the sympathoadrenal axis are prevented. SHRs and Wistar Kyoto (WK Y) rats were anesthetized and administered 20 ml/kg 0.9% saline, and an inf usion of aldosterone and hydrocortisone was initiated. After bilateral adre nalectomy, left renal denervation, and pretreatment with captopril, animals received an intrarenal artery infusion of Ang II at 10 ng/kg/min for 5 min . Ang II-induced changes in renal vascular resistance were greater in SHRs compared with WKY rats (p = .010, n = 19/group). Pertussis toxin (10 mu g/k g i.v. 3 days before the experiment) attenuated Ang II-induced changes in r enal vascular resistance in SHR (p<.05), but not in WKY rats (strain 3 trea tment interaction: p = .046). These results suggest that the enhanced renov ascular response to Ang II in SHRs is mediated by a G(i)-dependent pathway within the renal vasculature.