RESUMO
Background: Continuous nitrate therapy leads to complete tolerance within 24 to 48 hours. The mechanism[s] responsible for nitrate tolerance is unclear, but there is increasing evidence that nitroglycerin [NTG] leads to superoxide anion production. Estrogen re-placement exerts a cardioprotective effect in postmenopausal women, one of its beneficial effects is to scavenge superoxide radicals
Objectives: This study sought to evaluate the preventive effect of trasdermal estrogen [TD-E] on the development of nitrate tolerance
Methods: In this double-blind, placebo-controlled study, 30 post-menopausal women with chronic stable angina pectoris [mean age 60 +/- 9 years] were randomized to receive either TD-E patch [delivering 50 mg daily] [estradiol group, n = 15] or placebo [placebo group, n = 15]. The vasodilator response to NTG was assessed by measuring the change in brachial artery diameter before and 5 min after 0.5 mg sublingual NTG, using a high resolution ultrasound. Blood samples were simultaneously obtained to measure serum estradiol levels. Brachial artery study and blood sampling were performed serially at baseline [day 0], 3 days after administration of TD-E or placebo [day 3] and 3 days after application of a 5-mg/bid NTG tape concomitantly with TD-E or placebo [day 6]
Results: There was no significant difference in NTG-mediated dilatation between the placebo group and the estradiol group on day 0 [estradiol group, 22.1 +/- 3.6 %; placebo group, 21.8 +/- 5.7 %] or day 3 [estradiol group 22.8 +/- 3.7 %; placebo group 22 +/- 4.8 %]. On day 6, the NTG mediated dilatation in the placebo group [9.5 +/- 2.4 %] was significantly reduced compared with that on days 0 and 3 [p < 0.01]. By contrast, in the estradiol group, the NTG-mediated dilatation [23.1 + 2.1%] was maintained and significantly greater than that in the placebo group [p < 0.01]. Estradiol maintained also the hemodynamic effect of NTG despite its continuous application
Conclusions: Our findings suggest that TD-E patches attenuate nitrate tolerance in postmenopausal women with chronic stable angina. Although the underlying mechanism has not been determined, the estrogenic antioxidant effects provide an attractive explanation