McMullen J R, Gibson K J, Lumbers E R, Burrell J H, Wu J
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
Eur J Pharmacol. 1999 Aug 6;378(2):195-202. doi: 10.1016/s0014-2999(99)00454-9.
This study was performed to investigate the roles of angiotensin receptors (AT1 and AT2) 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 microM) 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 AT2 antagonist enhanced (P < 0.05) the contractile responses to angiotensin II, suggesting that angiotensin AT2 receptors inhibited the angiotensin AT1 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 AT2 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 AT2 receptors. It is concluded that in normal pregnancy angiotensin AT2 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 AT1 receptors are down regulated.
本研究旨在探讨血管紧张素受体（AT1和AT2）在正常妊娠期间及血管紧张素II水平升高后子宫动脉收缩性中的作用。给怀孕母羊静脉输注生理盐水24小时（对照组）或血管紧张素II（30 ng kg⁻¹ min⁻¹）2小时或24小时。然后在体外检测子宫动脉环对血管紧张素II（4 μM）和拮抗剂的收缩反应。大多数子宫动脉对血管紧张素II的血管收缩作用相对不敏感。在对照组母羊的动脉环中，血管紧张素AT2拮抗剂增强了（P < 0.05）对血管紧张素II的收缩反应，表明血管紧张素AT2受体抑制了血管紧张素AT1受体介导的收缩。与对照组母羊的动脉环相比，静脉输注血管紧张素II的母羊的子宫动脉环在体外对血管紧张素II表现出更大的（P < 0.05）收缩反应。这部分是由于血管紧张素AT2受体的下调。令人惊讶的是，在进行这些实验时，少数母羊的子宫动脉对血管紧张素II“反应过度”（收缩反应大6倍）。这些母羊还具有异常的肾素血管紧张素系统，并且具有一些子痫前期所见的特征。这些动脉的“反应过度”只能部分地由血管紧张素AT2受体的下调来解释。结论是，在正常妊娠中，血管紧张素AT2受体在维持胎儿充足的子宫血流中起作用。当血管紧张素II水平长期升高时，这种保护作用部分丧失，因为血管紧张素AT1受体被下调。
