Estrogen-induced improvement in coronary flow responses during atrial pacing in relation to endothelin-1 levels in postmenopausal women without coronary disease

BACKGROUND: The cardioprotective role of hormonal replacement therapy remains in doubt, but interest is increasing in the vascular effects of estrogens especially in coronary circulation. METHODS: Coronary blood flow (CBF) was measured in 24 postmenopausal women (age 55 ± 3 years), whose coronary arteries appeared angiographically normal, during incremental atrial pacing (AP) before and 20 minutes after intracoronary administration of either 75 ng/mL 17-β estradiol (treated group, n = 18) or 0.9% saline (controls, n = 6). RESULTS: Before estrogen, no differences in the coronary vasomotor responses at AP between the two groups (p = NS) could be detected. After estrogen, in the treated group, at the peak of the second AP, the coronary artery diameter decreased by 0.17 mm (p < 0.005) while the CBF increased by 61 mL/min (p < 0.05). These changes differed significantly from those observed at the peak of first AP (p < 0.001 for both cases). In contrast, in the control group no such changes were observed. The endothelin-1 (ET-1) levels in the coronary sinus were significantly reduced after estrogen infusion, which was negatively correlated with the degree of coronary artery constriction (r = −0.40, p = 0.03) and positively correlated with the increase in CBF (r = 0.54, p = 0.01). CONCLUSIONS: In postmenopausal women without coronary artery disease, the intracoronary estrogen infusion mediates a greater increase in CBF and is positively correlated with the reduction of the coronary sinus ET-1 levels at the peak of AP.