Angiotensin II receptor alterations during pregnancy in rabbits

Despite activation of the renin-angiotensin system during pregnancy, renal and peripheral vascular blood flows increase, and the systemic blood pressure and the pressor response to exogenous angiotensin II (Ang II) fall. Gestational alterations in Ang II receptors could contribute to these changes. Ang II binding parameters were determined utilizing ¹²⁵I-Ang II in vascular (glomeruli and mesenteric arteries) and nonvascular (adrenal glomerulosa) tissues from 24- to 28-day pregnant rabbits. Comparisons were made utilizing tissues from nonpregnant rabbits. Binding site concentrations (N) and dissociation constants (K(d)) were obtained by Scatchard analyses of binding inhibition data. In glomeruli from nonpregnant and pregnant rabbits, N was 515 ± 84 and 300 ± 54 fmol.mg^-1 protein (P < 0.005; n = 8), respectively. K(d) did not differ (P > 0.05). In mesenteric artery membranes from nonpregnant (n = 3) and pregnant (n = 4) rabbits, N was 304 ± 21 and 112 ± 23 fmol.mg^-1 (P < 0.005), respectively. K(d) did not differ. Neither N nor K(d) differed in adrenal glomerulosa tissues (n = 6). Meclofenamate (M) inhibits prostaglandin synthesis, reduces plasma renin activity, and enhances the pressor response to infused Ang II in pregnant rabbits. Administration of M to pregnant rabbits increased N in glomerular and in mesenteric artery membranes from 298 ± 16 to 381 ± 8 fmol.mg^-1 (n = 3) and from 144 ± 13 to 218 ± 13 fmol.mg^-1 (n = 4), respectively. These data demonstrate that Ang II receptors in glomeruli and mesenteric arteries are down regulated during gestation in rabbits. Elevated endogenous Ang II during pregnancy in rabbits may contribute to the down regulation of vascular Ang II receptors.