title: Pregnancy and estradiol decrease GTPase activity in the guinea pig uterine artery.
abstract: The mechanisms by which pregnancy redistributes cardiac output in an organ-specific manner are poorly understood. We propose that it is consequential to estrogen-mediated alterations in G protein-mediated signal transduction. Aortas and uterine (UAs) and mesenteric arteries (MAs) were obtained from late-pregnant, nonpregnant, or ovariectomized guinea pigs chronically treated with 17beta-estradiol. High-affinity GTPase activity was assayed enzymatically. The cGMP generated in response to the endothelium-dependent agonist ACh was measured in UAs incubated with or without cholera toxin (CTX, which inhibits G(s)alpha). Pregnancy significantly decreased UA but not aorta or MA GTPase activity. 17beta-Estradiol decreased UA GTPase activity compared with untreated ovariectomized animals. ACh increased cGMP in pregnant but not nonpregnant UAs. Pretreatment of nonpregnant UAs with CTX increased ACh-induced cGMP levels similar to pregnancy. Thus pregnancy and estradiol decrease the GTPase activity of a CTX-sensitive G protein in UAs, increasing receptor-dependent cGMP release. This alteration in receptor-mediated G protein coupling in UAs may contribute to the characteristic cardiovascular adaptation to pregnancy.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201-1559, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Buhimschi
authors.forename: G
authors.initials: G
authors.lastname: Hall
authors.forename: L P
authors.initials: LP
authors.lastname: Thompson
authors.forename: C P
authors.initials: CP
authors.lastname: Weiner
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006168:Guinea Pigs; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D014599:Uterus / Q000098:blood supply*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D014665:Vasodilator Agents; D009569:Nitric Oxide; D004958:Estradiol; D002772:Cholera Toxin; D020558:GTP Phosphohydrolases; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin