title: Differential effects of mineralocorticoid blockade on the hypothalamo-pituitary-adrenal axis in pregnant and nonpregnant ewes.
abstract: During pregnancy, plasma ACTH and cortisol are chronically increased; this appears to occur through a reset of hypothalamo-pituitary-adrenal (HPA) activity. We have hypothesized that differences in mineralocorticoid receptor activity in pregnancy may alter feedback inhibition of the HPA axis. We tested the effect of MR antagonism in pregnant and nonpregnant ewes infused for 4 h with saline or the MR antagonist canrenoate. Pregnancy significantly increased plasma ACTH, cortisol, angiotensin II, and aldosterone. Infusion of canrenoate increased plasma ACTH, cortisol, and aldosterone in both pregnant and nonpregnant ewes; however, the temporal pattern of these responses differed between these two reproductive states. In nonpregnant ewes, plasma ACTH and cortisol transiently increased at 1 h of infusion, whereas in pregnant ewes the levels gradually increased and were significantly elevated from 2 to 4 h of infusion. MR blockade increased plasma aldosterone from 2 to 4 h in the pregnant ewes but only at 4 h in the nonpregnant ewes. In both pregnant and nonpregnant ewes, the increase in plasma aldosterone was significantly related to the timing and magnitude of the increase in plasma potassium. The results indicate a differential effect of MR activity in pregnant and nonpregnant ewes and suggest that the slow changes in ACTH, cortisol, and aldosterone are likely to be related to blockade of MR effects in the kidney rather than to effects of MR blockade in hippocampus or hypothalamus.
authors.affiliation: Dept. of Pharmacodynamics, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lingis
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Richards
authors.forename: Maureen
authors.initials: M
authors.lastname: Keller-Wood
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001810:Blood Volume / Q000502:physiology; D002191:Canrenoic Acid / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006400:Hematocrit; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D012756:Sheep; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D011374:Progesterone; D002191:Canrenoic Acid; D000324:Adrenocorticotropic Hormone