Daidzein and 17 beta-estradiol enhance nitric oxide synthase activity associated with an increase in calmodulin and a decrease in caveolin-1.
Isoflavones, such as daidzein, are proposed to possess vasculoprotective properties, perhaps through a mechanism similar to estrogen. Our experiments aimed to test the hypothesis that daidzein and 17 beta-estradiol enhance endothelium-dependent relaxation through an increase in NO synthesis due to an increase in activity or expression of endothelial nitric oxide synthase (eNOS). Male rats were treated with daidzein (0.2 mg/kg per day sc), 17 beta-estradiol (0.1 mg/kg per day sc), or vehicle for 7 days and reactivity of isolated aortic rings was then determined. ACh-induced relaxation was significantly enhanced in aortic rings from rats treated with daidzein or 17 beta-estradiol but the relaxant responses to the endothelium-independent dilators sodium nitroprusside or isoprenaline were not different. Nitrite production and the level of cGMP were significantly greater in aortae from daidzein and 17 beta-estradiol compared with vehicle-treated rats. Daidzein and 17 beta-estradiol did not alter eNOS protein in endothelium-intact aortae but reduced expression of caveolin-1 and increased expression of calmodulin, changes that would account for an increase in eNOS activity. There were no differences between groups in the expression of calmodulin and caveolin-1 in arteries when the endothelium was removed. Daidzein or 17 beta-estradiol treatment selectively enhances endothelium-dependent relaxation in male rats through an increase in eNOS activity. The increase in eNOS activity is associated with a decreased expression of caveolin-1 and an increased expression of calmodulin in endothelial cells.
Woodman
Owen L
OL
Department of Pharmacology, University of Melbourne, Victoria, Australia. owenlw@unimelb.edu.au
Missen
Melinda A
MA
Boujaoude
Mirna
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006152:Cyclic GMP / Q000737:chemistry / Q000378:metabolism; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007279:Injections, Subcutaneous; D007529:Isoflavones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects
D002147:Calmodulin; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D007529:Isoflavones; D010643:Phenoxybenzamine; D009599:Nitroprusside; D019335:Nitroarginine; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; C004742:daidzein; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006152:Cyclic GMP; D007545:Isoproterenol; D000109:Acetylcholine