Effects of combined use of sildenafil citrate (Viagra) and 17β-estradiol on ovine coronary and uterine hemodynamics

Abstract

Objective This study was undertaken to determine whether Viagra (Pfizer, New York, NY), a type 5 phosphodiesterase (PDE-5) inhibitor, increases baseline coronary and uterine blood flow or potentiates estrogen-induced increases in blood flow. Study design Seven nonpregnant ovariectomized ewes were chronically instrumented to measure blood pressure, heart rate, cardiac output, and coronary and uterine blood flow. Estradiol-17β (E2, 0.3 μg/kg) (Sigma Chemical Co, St Louis, Mo) and Viagra (50 mg) were intravenously administered separately or together and hemodynamic responses monitored. Results Viagra alone rapidly decreased mean arterial pressure and cardiac output while increasing heart rate and uterine blood flow. Viagra tended to decrease coronary blood flow but not significantly. E2 by itself increased coronary and uterine blood flow over a 2-hour time course, whereas mean arterial pressure, cardiac output, and heart rate remained unchanged. Administration of E2 to animals pretreated with Viagra reversed Viagra-related decrease in cardiac output and coronary blood flow, resulting in a time-related increase in both parameters over baseline values. Viagra significantly augmented estradiol-related increases in uterine blood flow. Conclusion In our surgically menopausal ovine model, Viagra alone has a tendency to decrease baseline coronary blood flow, but the reduction does not reach statistical significance. The presence of estradiol reverses this Viagra-related negative trend and results in a net increase in coronary blood flow and cardiac output. Furthermore, Viagra significantly augments baseline and estrogen-induced increases in uterine blood flow suggesting the presence of PDE-5 in the ovine uterine vasculature.