title: Effect of 17-beta estradiol in the rabbit: endothelium-dependent and -independent mechanisms of vascular relaxation.
abstract: Short-term estrogen administration has been independently proposed to produce arterial vasodilation by both an indirect mechanism and a direct mechanism (inhibition of calcium entry though the L-type calcium channel). The proposed contributions of such diverse mechanisms to the vascular actions of 17beta-estradiol were examined in perfused hearts and in aortic ring sections isolated from female rabbits. In isolated rabbit hearts retrogradely perfused with Tyrode's solution, concentration-response curves to 17beta-estradiol (10(-9)-10(-5) M) were performed under control conditions and during perfusion with Bay K8644 (10(-7) M). 17beta-Estradiol produced a concentration-dependent decrease in coronary vascular resistance proportional to nitric oxide (NO) release in the presence and absence of Bay K8644. The addition of N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) to the perfusate (a) completely inhibited NO formation, (b) produced a 2.3-fold and 1.55-fold rightward shift in the concentration-response curve to 17beta-estradiol for Bay K8644 treated and control hearts, respectively, and (c) failed to prevent coronary artery vasodilation. In isolated aortic rings contracted with Bay K8644, 17beta-estradiol (10(-5) M) relaxed both intact (58%) and denuded (54%) aortic rings. L-NAME (10(-4) M) completely blocked NO release in intact rings but did not prevent relaxation in denuded aortic rings. The data demonstrate (a) an endothelium-dependent relaxation by 17beta-estradiol, coincident with NO formation and suppressed by L-NAME, and (b) a direct relaxation of aortic and coronary smooth muscle independent of NO formation at higher 17beta-estradiol concentrations.
authors.affiliation: Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City 73190, U.S.A.
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: C P
authors.initials: CP
authors.lastname: Robinson
authors.forename: U
authors.initials: U
authors.lastname: Thadani
authors.forename: E
authors.initials: E
authors.lastname: Patterson
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D002120:Calcium Channel Agonists; D009569:Nitric Oxide; D004958:Estradiol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester