Acute administration of 17β-estradiol reduces endothelin-1 release during pacing-induced ischemia

Objectives To assess whether acute administration of 17β-estradiol reduces pacing-induced cardiac release of endothelin-1 in female menopausal patients with coronary artery disease. Background Endothelin-1 is a potent vasoactive peptide which plays a pathogenetic role in myocardial ischemia and adverse clinical events in patients with coronary artery disease. Estrogens decrease plasma levels of endothelin-1 and improve stress-induced myocardial ischemia in menopausal women with coronary artery disease. Methods Twenty-two postmenopausal women with angiographically proven coronary artery entered a randomized, double blinded, placebo-controlled study. Patients were sampled into the coronary sinus and aorta for endothelin-1 at baseline and after incremental pacing. After baseline study, patients were randomized to receive either sublingual 17β-estradiol (1 mg) or placebo and underwent the sampling protocol 20 min thereafter. Results 17β-Estradiol but not placebo improved the time of onset of myocardial ischemia during pacing. The coronary sinus plasma levels of endothelin-1 were significantly reduced by estradiol administration but not by placebo, at each step of pacing protocol. The maximum reduction of endothelin-1 was noted at peak pacing (− 0.18 ng/l; − 0.09, − 0.3; 95% CI). No changes in endothelin-1 were noted in patients allocated to placebo ( −0.002 ng/l; − 0.06, − 0.01; 95% CI). Similarly, aorto-coronary sinus difference of endothelin-1 was significantly influenced by 17β-estradiol administration but not by placebo. Conclusion Acute administration of 17β-estradiol reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with coronary artery disease. This result may be related to the anti-ischemic or to a primary direct effect of the hormone upon myocyte release of the peptide, and may contribute to its anti-ischemic effect. Condensed abstract To assess effect of acute 17β-estradiol administration on pacing-induced cardiac release of endothelin-1, we studied 22 female menopausal patients with coronary artery diseases. In a randomized, double-blinded, placebo-controlled study, patients were randomized to receive either sublingual 17β-estradiol (1 mg) or placebo. Aortic and coronary sinus plasma endothelin-1 levels were evaluated at baseline, during incremental atrial pacing, and at peak pacing before and after the sublingual administration of either 17β-estradiol or placebo. The time to the onset of myocardial ischemia during pacing was significantly increased by 17β-estradiol vs. placebo. Moreover, coronary sinus endothelin-1 levels at peak pacing and aortic-coronary sinus changes were significantly improved by the administration of 17β-estradiol but not by placebo. Acute administration of 17β-estradiol reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with coronary artery disease.