ANGIOTENSIN-II VASCULAR SMOOTH-MUSCLE RECEPTORS ARE NOT DOWN-REGULATED IN NEAR-TERM PREGNANT SHEEP

Normal human and ovine pregnancies are associated with elevated plasma angiotensin II levels and refractoriness to the vasoconstrictor effects of infused angiotensin II, which is greater in the ovine uteroplacental vascular bed than in the systemic vasculature. It remains unclear whether this refractoriness reflects alterations in angiotensin II vascular smooth-muscle receptor density or affinity. We examined the angiotensin II vascular smooth-muscle receptor in nonpregnant (n = 12) and near-term pregnant (130 +/- 3 days [mean +/- SD], n = 10) sheep, comparing binding characteristics on plasma membranes prepared from the medial layer of aorta, mesenteric artery, and uterine artery. Plasma angiotensin II levels were increased threefold to fourfold (P < 0.001) in pregnant ewes. A single class of high-affinity angiotensin II vascular smooth-muscle receptor was identified in each type of artery. Receptor density was similar in nonpregnant and pregnant mesenteric artery (92 +/- 21 vs 103 +/- 40 fmol/mg protein, respectively), aorta (186 +/- 29 vs 220 +/- 46 fmol/mg protein), and uterine artery (59 +/- 20 vs 77 +/- 20 fmol/mg protein) tissue. Receptor affinity also was unchanged during pregnancy. Because changes in the density and affinity of the angiotensin II vascular smooth-muscle receptor were not observed in near-term pregnant ewes, the attenuated vasoconstrictor responses seen during pregnancy do not reflect receptor down-regulation or decreased affinity.