Blockade of angiotensin receptor subtypes in arcuate uterine artery of pregnant and postpartum rats

During pregnancy, uterine circulation undergoes hypertrophy and hyperplasia . We investigated the effects of angiotensin (Ang) II receptor subtype (AT( 1)/AT(2)) blockade on increased responses to the peptide during reversible remodeling of the uterine vasculature in pregnant and postpartum rats. Uter ine arcuate arteries were set up in wire myographs for microvessel and subm itted to a tension equivalent to 50 mm Hg transmural pressure. Cumulative c oncentration-response curves to Ang II were measured in the absence and pre sence of losartan on the same vascular segment. A similar protocol was repe ated in the presence of PD 123,319, an AT(2) receptor blocker, again in the absence and presence of losartan. Responses to Ang II on the arcuate arter y increased markedly during pregnancy and returned to the prepregnant level within 12 days postpartum. Losartan (10(-7) mol/L) produced a parallel rig ht shift of the concentration-response curve to Ang II in all groups of tis sues, but potency of the AT, receptor blocker was reduced at the end of pre gnancy and in the early postpartum period. PD 123,319 (10(-7) mol/L) signif icantly increased maximum response to Ang II in arterial segments of the no npregnant, term-pregnant, and 5 days postpartum rats. AT(1) receptor expres sion was decreased in arcuate arteries of term-pregnant rats. These results show that contractile responses to Ang II on the uterine arcuate artery of the rat are mediated by the AT(1) receptor and that blockade of AT(2) rece ptors potentiated responses to the peptide. They also indicate that, in ute rine vessels, AT(2) receptor stimulation interferes with Ang II responses, but this effect is decreased in uterine arcuate arteries in the peripartum period.