Pregnancy and estradiol decrease GTPase activity in the guinea pig uterineartery

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 treat ed with 17 beta -estradiol. High-affinity GTPase activity was assayed enzym atically. The cGMP generated in response to the endothelium-dependent agoni st ACh was measured in UAs incubated with or without cholera toxin (CTX, wh ich inhibits Gsa). Pregnancy significantly decreased UA but not aorta or MA GTPase activity. 17 beta -Estradiol decreased UA GTPase activity compared with untreated ovariectomized animals. ACh increased cGMP in pregnant but n ot nonpregnant UAs. Pretreatment of nonpregnant UAs with CTX increased ACh- induced cGMP levels similar to pregnancy. Thus pregnancy and estradiol decr ease the GTPase activity of a CTX-sensitive G protein in UAs, increasing re ceptor-dependent cGMP release. This alteration in receptor-mediated G prote in coupling in UAs may contribute to the characteristic cardiovascular adap tation to pregnancy.