EFFECT OF 17-BETA ESTRADIOL IN THE RABBIT - ENDOTHELIUM-DEPENDENT ANDENDOTHELIUM-INDEPENDENT MECHANISMS OF VASCULAR RELAXATION

Short-term estrogen administration has been independently proposed to produce arterial vasodilation by both an indirect mechanism and a dire ct mechanism (inhibition of calcium entry though the L-type calcium ch annel). The proposed contributions of such diverse mechanisms to the v ascular actions of 17 beta-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, concentrat ion-response curves to 17 beta-estradiol (10(-9)-10(-5) M) were perfor med under control conditions and during perfusion with Bay K8644 (10(- 7) M). 17 beta-Estradiol produced a concentration-dependent decrease I n coronary vascular resistance proportional to nitric oxide (NO) relea se in the presence and absence of Bay K8644. The addition of N-G-nitro -L-arginine methyl eater (L-NAME; 10(-4) M) to tile perfusate (a) comp letely inhibited NO formation, (b) produced a 2.3-fold and 1.55-fold r ightward shift in the concentration-response curve to 17 beta-estradio l for Bay K8644 treated and control hearts, respectively, and (c) fail ed to prevent coronary artery vasodilation. In isolated aortic rings c ontracted with Bay K8644, 17 beta-estradiol (10(-5) M) relaxed both in tact (58%) and denuded (54%) aortic rings. L-NAME (10(-4) M) completel y blocked NO release in intact rings but did not prevent relaxation in denuded aortic rings. The data demonstrate (a) an endothelium-depende nt relaxation by 17 beta-estradiol, coincident with NO formation and s uppressed by L-NAME, and (b) a direct relaxation of aortic and coronar y smooth muscle independent of NO formation at higher 17 beta-estradio l concentrations.