doi: 10.1161/hy1101.095008
(Hypertension. 2001;38:1017.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Blockade of Angiotensin Receptor Subtypes in Arcuate Uterine Artery of Pregnant and Postpartum Rats
From the Laboratoire de Pharmacologie Vasculaire Périnatale, Centre de Recherche Mère-Enfant, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Correspondence to Jean St-Louis, PhD, Centre de Recherche, Hôpital Sainte-Justine, 3175 Chemin Côte Ste-Catherine, Montréal, Québec H3T1C5, Canada. E-mail stlouisj{at}justine.umontreal.ca
Abstract—— During pregnancy, uterine circulation undergoes hypertrophy and hyperplasia. We investigated the effects of angiotensin (Ang) II receptor subtype (AT1/AT2) blockade on increased responses to the peptide during reversible remodeling of the uterine vasculature in pregnant and postpartum rats. Uterine arcuate arteries were set up in wire myographs for microvessel and submitted to a tension equivalent to 50 mm Hg transmural pressure. Cumulative concentration-response curves to Ang II were measured in the absence and presence of losartan on the same vascular segment. A similar protocol was repeated in the presence of PD 123,319, an AT2 receptor blocker, again in the absence and presence of losartan. Responses to Ang II on the arcuate artery increased markedly during pregnancy and returned to the prepregnant level within 12 days postpartum. Losartan (10-7 mol/L) produced a parallel right shift of the concentration-response curve to Ang II in all groups of tissues, but potency of the AT1 receptor blocker was reduced at the end of pregnancy and in the early postpartum period. PD 123,319 (10-7 mol/L) significantly increased maximum response to Ang II in arterial segments of the nonpregnant, term-pregnant, and 5 days postpartum rats. AT1 receptor expression 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 AT1 receptor and that blockade of AT2 receptors potentiated responses to the peptide. They also indicate that, in uterine vessels, AT2 receptor stimulation interferes with Ang II responses, but this effect is decreased in uterine arcuate arteries in the peripartum period.
Key Words: angiotensin • receptors, angiotensin • arteries, uterine • losartan • pregnancy
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