Interactions between AT 1 and AT 2 receptors in uterine arteries from pregnant ewes

Abstract

This study was performed to investigate the roles of angiotensin receptors (AT 1 and AT 2) in the contractility of uterine arteries during normal pregnancy and after angiotensin II levels have been elevated. Pregnant ewes were given intravenous infusions of saline for 24 h (control) or angiotensin II (30 ng kg −1 min −1) for 2 or 24 h. The contractile responses of uterine arterial rings to angiotensin II (4 μM) and antagonists were then examined in vitro. Most uterine arteries were relatively insensitive to the vasoconstrictor effects of angiotensin II. In rings from control ewes an angiotensin AT 2 antagonist enhanced ( P<0.05) the contractile responses to angiotensin II, suggesting that angiotensin AT 2 receptors inhibited the angiotensin AT 1 receptor mediated contractions. Uterine arterial rings from ewes given intravenous infusions of angiotensin II displayed greater ( P<0.05) contractile responses to angiotensin II in vitro compared to rings from control ewes. This was in part due to down regulation of angiotensin AT 2 receptors. Surprisingly, while performing these experiments a small number of ewes had uterine arteries which were “hyperreactive” to angiotensin II (contractile responses 6-fold greater). These ewes also had abnormal renin angiotensin systems and had some features which are characteristic of those seen in preeclampsia. The “hyperreactivity” of these arteries could only in part be explained by down regulation of angiotensin AT 2 receptors. It is concluded that in normal pregnancy angiotensin AT 2 receptors play a role in maintaining an adequate uterine blood flow for the fetus. When angiotensin II levels are elevated for a prolonged period this protective effect is lost partly because angiotensin AT 2 receptors are down regulated.