title: Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in rat hearts.
abstract: Previous studies have shown that estrogen modulation of endothelial nitric oxide (NO) synthase (eNOS) may confer protection against heart disease. Here, we demonstrate an association between reductions in baroreflex-mediated bradycardia and in cardiac NOS activity in ovariectomized (Ovx) rats compared with controls. The latter resulted, at least in part, from a reduction in cardiac eNOS protein. eNOS-derived NO and its biological effects are determined by the levels of eNOS protein and by eNOS catalytic activity; the latter is regulated partly through the dynamic interaction with an inhibitory protein (caveolin) and a stimulatory protein (calmodulin). The association of eNOS immunoprecipitated with caveolin-3 and calmodulin was examined. Caveolin-3 and calmodulin binding with eNOS was increased and decreased, respectively, in Ovx rats. 17 beta-Estradiol replacement restored, to within normal levels, the baroreflex-mediated bradycardic responses along with eNOS activity, eNOS expression, and the association of eNOS with caveolin-3 and calmodulin. Our findings may help to elucidate the molecular mechanism underlying the favorable effects of estrogen on cardiac responses to baroreflex activation.
authors: Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
authors: Xu
authors: X
authors: Wang
authors: Abdel A
authors: AA
authors: Abdel-Rahman
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000201:enzymology; D002147:Calmodulin / Q000378:metabolism*; D051244:Caveolin 3; D022461:Caveolins / Q000378:metabolism*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002147:Calmodulin; C495549:Cav3 protein, rat; D051244:Caveolin 3; D022461:Caveolins; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat