ROLE OF ANGIOTENSIN RECEPTOR SUBTYPES IN THE RESPONSE OF RABBIT BRAIN ARTERIOLES TO ANGIOTENSIN

Background and Purpose Angiotensin II has been reported to induce either constriction or dilation in the cerebral microcirculation. The goal of this study was to determine whether binding to different angiotensin II receptor subtypes may account for the divergent responses. Methods Pial arterioles ranging in diameter from 28 to 136 I-Lm were observed through a microscope in a closed cranial window preparation in anesthetized rabbits. Arteriolar responses to topical application of 10(-5) mol/L angiotensin II or the vasoactive angiotensin II degradation products L-arginine/ angiotensin-(3-8) were measured by videometry. The effect of the subtype 1 receptor antagonist losartan and the subtype 2 antagonist PD 123319 on these responses was examined in separate groups of animals. Results Topical coapplication of 10(-5) mol/L losartan or 10(-5) mol/L PD 123319 produced 55% and 62% inhibition of the dilator response to 10(-5) mol/L angiotensin II, respectively. Combined application of the antagonists caused 79% inhibition. Each of the antagonists almost completely blocked the response to L-arginine/angiotensin-(3-8). Acetylcholine-induced dilation of rabbit brain arterioles was unaffected by the antagonists. Conclusions Both of the known angiotensin II receptor subtypes appear to be involved in angiotensin II-induced dilation of rabbit cerebral arterioles. These results argue against the assumption that vasodilation is a specific function of one of these receptor subtypes, which might have explained the equivocal effects of angiotensin II by predominance of a certain receptor subtype in a given vascular bed.