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Acute administration of 17beta-estradiol reduces endothelin-1 release during pacing-induced ischemia
Giuseppe M C Rosano1, Otavio Gebara, Imad Sheiban
1Cardiovascular Research Unit, IRCCS San Raffaele Roma, Via della Pisana, 235 00163, Roma, Italy. giuseppe.rosano@sanraffaele.it
Insights
Acute 17beta-estradiol administration effectively reduces cardiac endothelin-1 release in postmenopausal women with coronary artery disease. This finding suggests a potential therapeutic benefit of estrogen in managing myocardial ischemia.
Area of Science:
- Cardiovascular Endocrinology
- Reproductive Medicine
- Vascular Biology
Background:
- Endothelin-1 (ET-1) is implicated in myocardial ischemia and adverse events in coronary artery disease (CAD).
- Estrogens are known to lower ET-1 levels and improve stress-induced ischemia in postmenopausal women with CAD.
Purpose of the Study:
- To determine if acute 17beta-estradiol administration reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with CAD.
- To evaluate the impact of 17beta-estradiol on myocardial ischemia onset during pacing.
Main Methods:
- A randomized, double-blind, placebo-controlled study involving 22 postmenopausal women with confirmed CAD.
- Measurement of endothelin-1 in coronary sinus and aorta at baseline and during incremental pacing before and after sublingual administration of 17beta-estradiol or placebo.
Main Results:
- 17beta-estradiol significantly delayed the onset of myocardial ischemia during pacing compared to placebo.
- Estradiol administration led to a significant reduction in coronary sinus endothelin-1 levels at peak pacing.
- No significant changes in endothelin-1 levels were observed in the placebo group.
Conclusions:
- Acute 17beta-estradiol administration effectively reduces pacing-induced cardiac endothelin-1 release in postmenopausal women with CAD.
- This effect may contribute to the hormone's anti-ischemic properties, potentially through direct effects on myocyte peptide release.
Objectives:
To assess whether acute administration of 17beta-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 17beta-estradiol (1 mg) or placebo and underwent the sampling protocol 20 min thereafter.
Results:
17Beta-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 17beta-estradiol administration but not by placebo.
Conclusion:
Acute administration of 17beta-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 17beta-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 17beta-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 17beta-estradiol or placebo. The time to the onset of myocardial ischemia during pacing was significantly increased by 17beta-estradiol vs. placebo. Moreover, coronary sinus endothelin-1 levels at peak pacing and aortic-coronary sinus changes were significantly improved by the administration of 17beta-estradiol but not by placebo. Acute administration of 17beta-estradiol reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with coronary artery disease.
