Multiple mechanisms are involved in the acute vasodilatory effect of 17 beta-estradiol in the isolated perfused rat heart

The purpose of this study was to define the dose-dependent effects of 17 be ta-estradiol on coronary flow and cardiac function in isolated rat hearts a nd to identify the mechanisms involved in its vasodilator action. Hearts fr om female and male Wistar rats were perfused at constant pressure (100 mm H g). Stereoisomer specificity and the mechanism of vasodilation by 17 beta-e stradiol were examined in female rat hearts. Function was measured by a lef t ventricular (LV) balloon and coronary flow (CF) with an ultrasonic flowme ter. 17 beta-Estradiol at 10(-6), 5 x 10(-6), and 10(-5) M increased CF in female hearts by 5 +/- 2, 27 +/- 4 (p < 0.05 vs. baseline), and 40 +/- 4% ( p < 0.05 vs. baseline), respectively. The effect of 17 beta-estradiol in he arts from male rats was similar but less pronounced compared with females [ Delta CF 8 +/- 3, 19 +/- 3 (p < 0.05 vs. baseline)] and 25 +/- 7% (p < 0.05 vs, baseline; p < 0.05 vs, female 17 beta-estradiol). Maximum vasodilation by the stereoisomer 17 alpha-estradiol was significantly smaller [Delta CF 5 +/- 3, 4 +/- 3 (p < 0.05 vs. female 17 beta-estradiol) and 14 +/- 1% (p < 0.05 vs. baseline; p < 0.05 vs. female 17 beta-estradiol)] for 10(-6), 5 x 10(-6), and 10(-5) M. Pretreatment with the NO-synthesis inhibitor N-omeg a-methyl-L-arginine (10(-4) M) had no effect on the maximal vasodilator res ponse to 17 beta-estradiol (10(-5) M) [Delta CF 36 +/- 6% (p < 0.05 vs. bas eline)]. When hearts were pretreated with the prostaglandin-synthesis inhib itor diclofenac (10(-6) M), the maximal vasodilator effect of 17 beta-estra diol was partially attenuated [Delta CF 12 +/- 7% (p < 0.05 vs, female 17 b eta-estradiol)]. Similarly, pretreatment with the K-ATP(+)-blocker glibencl amide (10(-6) M) partially inhibited the maximal vasodilator effect of 17 b eta-estradiol [Delta CF 22 +/- 6% (p < 0.05 vs. baseline; p < 0.05 vs. fema le 17 beta-estradiol)]. Pretreatment with the Ca2+ channel antagonist nifed ipine (7.2 x 10(-8) M) completely blocked the vasodilator effect. In isolat ed perfused rat hearts, 17 beta-estradiol induced marked acute coronary vas odilation; this effect is in pare gender specific, and in female hearts, la rgely stereoisomer specific. The dilator effect is mediated predominantly b y calcium channel blockade, but prostaglandin release and K-ATP(+) channel activation also are involved. In the isolated pet-fused rat heart, NO produ ction does not contribute to the acute vasodilator effect of 17 beta-estrad iol.