Premium
Mechanisms of decreased pressor response to infused angiotensin II in the pregnant rat
Author(s) -
YANG Ye,
MACDONALD Graham J,
DUGGAN Karen A
Publication year - 1996
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.1996.tb00122.x
Subject(s) - medicine , endocrinology , gestation , receptor , angiotensin ii , pregnancy , angiotensin receptor , vascular remodelling in the embryo , renin–angiotensin system , biology , blood pressure , genetics
Summary: This study sought to investigate two possible mechanisms underlying the decrease in the pressor response to infused angiotensin II (Ang II) in pregnancy. First, whether vascular Ang II receptors show parallel regulatory changes to their uterine counterparts during pregnancy and thus if a decrease in vascular angiotensin receptor number might explain this phenomenon. Second, we investigated the possibility that the rate of clearance of Ang II from the plasma was accelerated in pregnancy as a basis for this loss of pressor sensitivity. For receptor studies age‐matched female Wistar‐Kyoto rats were exposed to an appropriate breeding male and killed at days 7, 14 and 21 of gestation. Aortic, glomerular and uterine receptor binding was determined by saturation analysis using 125 I(Sar 1 Ileu 8 ) Ang II. Binding site density and dissociation constants were derived using the iterative computer program LIGAND. Metabolic clearance studies were performed by the equilibrium infusion method in a separate group of rats on day 14 after exposure to the breeder. Uterine and vascular Ang II receptors showed different patterns of regulation during gestation. the uterine receptors increased 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 were maximal at day 14. Although the total or uncorrected metabolic clearance rate was increased during gestation ( P < 0.05) no significant difference was observed after correction for either bodyweight or glomerular filtration rate. We conclude that neither a decrease in vascular Ang II receptor number or affinity explains the loss of pressor sensitivity to infused Ang II. In addition, this phenomenon is not explained by an increase in the rate of removal of Ang II from the circulation.