Acute administration of 17beta-estradiol reduces endothelin-1 release during pacing-induced ischemia.
OBJECTIVE
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Rosano
Giuseppe M C
GM
Cardiovascular Research Unit, IRCCS San Raffaele Roma, Via della Pisana, 235 00163, Roma, Italy. giuseppe.rosano@sanraffaele.it
Gebara
Otavio
O
Sheiban
Imad
I
Silvestri
Antonello
A
Wajngarten
Mauricio
M
Vitale
Cristiana
C
Aldrighi
Jose M
JM
Aldrighi
Jose
J
Ramires
Antonio F
AF
Fini
Massimo
M
Mercuro
Giuseppe
G
D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology / Q000378:metabolism*
D019332:Endothelin-1; D004958:Estradiol