Effects of ACTH-induced hypertension in the pregnant ewe

Adrenocorticotropic hormone (ACTH; 5 microg/kg/ day) infused into 10 pregnant ewes (gestation age, 127-139 days) for 72 h caused an increase in arterial pressure within 1-2 h (p < 0.05), which was sustained for the rest of the experiment. Cardiac output was increased at 24 h (p < 0.05). Total peripheral resistance did not change. There were no changes in four pregnant ewes infused with 0.15 M saline at the same rate for 72 h. In ACTH-treated pregnant ewes, a relation between arterial pressure and plasma renin activity observed in nontreated pregnant ewes (r = 0.71; p = 0.0005) was no longer evident. Compared with nonsurgical pregnant ewes, total angiotensin II (Ang II)-receptor density in the uterine artery was decreased in ewes that had previously had surgery (p = 0.015) and further reduced in ACTH-treated ewes (p < 0.0005). This was due to a reduction in the AT2-receptor density, which was inversely related to plasma cortisol levels (r = 0.73; p < 0.03). AT1-receptor density and the affinities of the AT1 and AT2 receptors were unchanged. The correlation between plasma cortisol and AT2-receptor density in uterine blood vessels may partly explain why these receptors are downregulated after surgery.