Differential contractile responses and receptor properties of fetal systemic arteries and uterine arteries of pregnant sheep to angiotensin II: arteries with high proportions of AT2 receptors

Abstract

Uterine arteries from pregnant animals are one of only a few adult blood vessels which express predominantly AT2 receptors. Fetal systemic arteries also contain a high density of AT2 receptors. To assess whether fetal systemic arteries, like uterine arteries from pregnant animals, were relatively insensitive to angiotensin II (Ang II), we compared the contractile responses of fetal carotid arteries, as well as the receptor binding properties of fetal aortae, with those of uterine arteries from pregnant ewes. Ang II receptor binding properties were measured in arterial membrane preparations using 125I [Sar1Ile8] Ang II. Proportions of AT1 and AT2 receptors were determined by inhibiting 125I [Sar1Ile8] Ang II with losartan (AT1 antagonist) or PD 123319 (AT2 antagonist). Both fetal aortae and uterine arteries contained predominantly AT2 receptors. However, the AT2 receptor in fetal aortae had a higher affinity than that of the AT2 receptor in uterine arteries (P<0.05). The contractile responses of fetal carotid arterial rings and uterine arterial rings to Ang II (4 µM) with and without antagonists were examined in vitro. Despite having similar proportions of Ang II receptor subtypes, fetal arterial rings were more responsive to Ang II in vitro than uterine arterial rings (P<0.05), possibly because of their greater density of AT1 receptors. The recognised in vitro phenomenon of Ang II-induced tachyphylaxis was observed in uterine arterial rings but not fetal arterial rings. In addition, Ang II induced responses in fetal carotid rings were largely unaffected by losartan (1 mM) or PD 123319 (1 mM), whereas Ang II induced contractile responses of uterine arterial rings were inhibited by losartan (1 mM) and enhanced by PD 123319 (1 mM). Thus, it would appear that Ang II receptors in systemic arteries of fetal sheep may be functionally dissimilar to those in the uterine artery of pregnant sheep.