The midgestational maternal blood pressure decline is absent in mice lacking expression of the angiotensin II AT2 receptor

Abstract

The midgestational maternal blood pressure (BP) decrease is absent in mice treated with an angiotensin II AT2 receptor blocker. We tested the hypotheses that there would be 1) no midgestational decrease in maternal systolic BP (SBP) in AT2-/-mice, and 2) a pattern of increased AT2 and/or decreased AT1a mRNA expression in tissues from normal (wild-type, WT) mice, corresponding with SBP changes. Heart, aorta, placenta and kidney tissue were obtained from WT and AT2-/-mice before pregnancy and on gestational days (Gd) 5-6, 12-13 and 18-19. AT1a and AT2 mRNA expression was quantified. SBP was measured. SBP was significantly decreased in WT Gd12-13 mice, but did not change during pregnancy in AT2-/-mice. In WT mice, aortic AT1a mRNA expression levels were significantly higher at Gd12-13 and Gd18-19 compared with before pregnancy. AT1a kidney and heart mRNA did not change during pregnancy. There were no changes in AT2 mRNA expression. There was no distinct pattern of change in AT1a expression in AT2-/-mice. Placental AT1a and AT2 expression levels increased markedly between Gd12-13 and Gd18-19 in WT mice. We conclude that the AT2 receptor is essential for the midgestational SBP decline in WT mice. There is no consistent relationship between changes in tissue angiotensin II receptor mRNA expression and SBP in WT mice.

The effects of gestational age and maternal hypoxia on the placental renin angiotensin system in the mouse

“…While Mas1 increased over gestation, Agtr2 levels remain constant over pregnancy. This is in contrast to a previous study which reported placental Agtr2 levels to be higher at E18 than E12 [48] although the increase in Agtr2 levels over pregnancy were minimal compared to the increase in Agtr1a reported. Mas1 expression, which peaked at E18.5 in the current study, has not been previously localised in the placenta.…”

The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

“…To our knowledge, however, a potential role for CGRP has not been tested, e.g., by administration of CGRP antagonists in gravid animal models. Recent evidence supports an important contribution of the AT2 receptor in mediating the midterm decline in systolic blood pressure in mice (21,25) and in attenuating constrictor responses to phenylephrine in the aorta from gravid rats (182), thus suggesting a potential role for AT2 receptor activation in the renal vasodilation of pregnancy. Intriguingly, both histidine decarboxylase and its enzymatic product histamine, a potent vasodilator, were reported to be increased in the superficial cortex of gravid mice (135).…”

Role of Inflammation and the Angiotensin Type 2 Receptor in the Regulation of Arterial Pressure During Pregnancy in Mice

“…However, this study did not observe the normal midgestational decrease in arterial pressure in WT (C57BL/6) mice and consequently did not report an effect of AT 2 R deletion on arterial pressure during midgestation. Conversely, Chen et al 16 and Carey et al 17 have demonstrated that pharmacological and genetic AT 2 R deficiency abolishes the normal midgestational decrease in arterial pressure. However, these studies observed no effect of AT 2 R deficiency on arterial pressure during late gestation.…”

“…These findings extend previous observations of the arterial pressure-lowering effects of the AT 2 R during pregnancy. [16][17][18] Secondly, in AT 2 R-KO mice there was a phenotypic switch in the T cells infiltrating the kidney toward a proinflammatory phenotype, resulting in an increase in the renal Th1:Th2 ratio at Gd16. Moreover, the increase in the Th1:Th2 ratio was observed only in the kidneys of pregnant AT 2 R-KO mice, which markedly contrasted the reduced Th1:Th2 ratios in the circulation and placentae as per regular pregnancies.…”