Angiotensin receptors and pressor hyperresponsiveness in renal prehypertensive rabbits

Abstract

This study consisted of five different experiments with conscious rabbits. In experiment 1, the angiotensin II (ANG II) antagonist [Sar1-Ala8]ANG II infused iv into one-kidney rabbits with renal artery stenosis (RAS) of 3 days' duration, at a dose that blocked pressor responses to ANG II, did not decrease the exaggerated pressor responses to norepinephrine (NE). In experiment 2, captopril infused iv into one-kidney, 3-day, RAS rabbits blocked pressor hyperresponsiveness to NE, and the concurrent infusion of [Sar1-Ala8]ANG II did not reestablish pressor hyperresponsiveness, indicating that this ANG II analogue had no agonistic action to promote hyperresponsiveness to NE. In experiment 3, infusion of ANG II at a subpressor dose (6.7 pmol . min-1 . kg body wt-1) into normal rabbits resulted in pressor hyperresponsiveness to NE, which was blocked by [Sar1-Ala8]ANG II. Experiment 4 involved infusing [Sar1-Ala8]ANG II or [Sar1-Ile8]ANG II at various doses into 3-day RAS rabbits, to determine their abilities to attenuate the pressor responses to ANG II (100 ng/kg) and the pressor hyper-responses to NE (800 ng . min-1 . kg-1). [Sar1-Ile8]ANG II decreased the ANG II pressor responses at an ID50 dose of 64 +/- 5 (SEM) pmol . min-1 . kg-1 and attenuated the NE pressor hyper-response at an ID50 dose of 65 +/- 5 pmol . min-1 . kg-1; [Sar1-Ala8]ANG II diminished the ANG II pressor response at an ID50 dose of 757 +/- 247 and the NE pressor hyper-response at an ID50 dose of 10,061 +/- 944 pmol . min-1 . kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)