MECHANISMS OF DECREASED PRESSOR-RESPONSE TO INFUSED ANGIOTENSIN-II INTHE PREGNANT RAT

This study sought to investigate two possible mechanisms underlying th e decrease in the presser response to infused angiotensin II (Ang II) in pregnancy. First, whether vascular Ang II receptors show parallel r egulatory changes to their uterine counterparts during pregnancy and t hus if a decrease in vascular angiotensin receptor number might explai n this phenomenon. Second, we investigated the possibility that the ra te of clearance of Ang II from the plasma was accelerated in pregnancy as a basis for this loss of presser sensitivity. For receptor studies age-matched female Wistar-Kyoto rats were exposed to an appropriate b reeding male and killed at days 7, 14 and 21 of gestation. Aortic, glo merular and uterine receptor binding was determined by saturation anal ysis using I-125(Sar(1) Ileu(8)) Ang II. Binding site density and diss ociation constants were derived using the iterative computer program L IGAND. Metabolic clearance studies were performed by the equilibrium i nfusion method in a separate group of rats on day 14 after exposure to the breeder. Uterine and vascular Ang II receptors showed different p atterns of regulation during gestation. The uterine receptors increase d in number at day 7 (P<0.001), then decreased significantly (P<0.05). Receptor affinity was unchanged at day 7 but decreased significantly at day 14 (P<0.005). In contrast, in the aorta and glomeruli receptor affinity was unchanged throughout gestation, while receptor numbers we re maximal at day 14. Although the total or uncorrected metabolic clea rance rate was increased during gestation (P<0.05) no significant diff erence was observed after correction for either bodyweight or glomerul ar filtration rate. We conclude that neither a decrease in vascular An g II receptor number or affinity explains the loss of presser sensitiv ity to infused Ang II. In addition, this phenomenon is not explained b y an increase in the rate of removal of Ang II from the circulation.