Functional role of angiotensin II type 1 and 2 receptors in regulation of uterine blood flow in nonpregnant sheep

Abstract

The objective was to determine the receptor subtype of angiotensin II (ANG II) that is responsible for vasoconstriction in the nonpregnant ovine uterine and systemic vasculatures. Seven nonpregnant estrogenized ewes with indwelling uterine artery catheters and flow probes received bolus injections (0.1, 0.3 and 1 microg) of ANG II locally into the uterine artery followed by a systemic infusion of ANG II at 100 ng x kg(-1) x min(-1) for 10 min to determine uterine vasoconstrictor responses. Uterine ANG II dose-response curves were repeated following administration of the ANG II type 2 receptor (AT(2)) antagonist PD-123319 and then repeated again in the presence of an ANG II type 1 receptor (AT(1)) antagonist L-158809. In a second experiment, designed to investigate the mechanism of ANG II potentiation that occurred in the presence of AT(2) blockade, nonestrogenized sheep received a uterine artery infusion of L-158809 (3 mg/min for 5 min) prior to the infusion of 0.03 microg/min of ANG II for 10 min. ANG II produced dose-dependent decreases in uterine blood flow (P < 0.03), which were potentiated in the presence of the AT(2) antagonist (P < 0.02). Addition of the AT(1) antagonist abolished the uterine vascular responses and blocked ANG II-induced increases in systemic arterial pressure (P < 0.01). Significant uterine vasodilation (P < 0.01) was noted with AT(1) blockade in the second experiment, which was reversed by administration of the AT(2) antagonist or by the nitric oxide synthetase inhibitor N(omega)-nitro-L-arginine methyl ester. We conclude that the AT(1)-receptors mediate the systemic and uterine vasoconstrictor responses to ANG II in the nonpregnant ewe. AT(2)-receptor blockade resulted in a potentiation of the uterine vasoconstrictor response to ANG II, suggesting that the AT(2)-receptor subtype may modulate uterine vascular responses to ANG II potentially by release of nitric oxide.

Pregnancy and Ovarian Steroid Regulation of Angiotensin II Type 1 and Type 2 Receptor Expression in Ovine Uterine Artery Endothelium and Vascular Smooth Muscle

“…There has been extensive study of the regulation of AT receptors in the VSM of uterine and systemic arteries (Cox et al 1996b;Burrell and Lumbers 1997;Rosenfeld 2001). Many studies associate activation of the AT 1 R on VSM as being responsible for constriction of the vessel (Chiu et al 1991;Timmermans et al 1993), although involvement of the AT 2 R in vessel tone has been observed as well (Lambers et al 2000). We investigated the expression of AT 1 R in VSM of UA, and as a systemic control to establish specificity of response to the UA, we used OA Endo and VSM (Figure 2).…”

Vascular angiotensin II actions mediated by angiotensin II type 2 receptors

“…Using anesthetized rat preparations, AT 2 R-mediated vasodilation has been reported in coronary, uterine, and renal vascular beds [32][33][34]. Recently, the effects of AT 2 R stimulation were examined in hemodynamically instrumented conscious SHR and WKY rats, in which renal, mesenteric, and hindquarter circulations were simultaneously measured.…”