Sildenafil inhibits β-adrenergic-stimulated cardiac contractility in humans

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-10, Vol.112 (17), p.2642-2649
• Main Authors: BORLAUG, Barry A, MELENOVSKY, Vojtech, MARHIN, Tricia, FITZGERALD, Patricia, KASS, David A
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cyclic Nucleotide Phosphodiesterases, Type 5; Diastole - drug effects; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dobutamine - pharmacology; Double-Blind Method; Electrocardiography; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Medical sciences; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Phosphodiesterase Inhibitors - pharmacology; Piperazines - blood; Piperazines - pharmacology; Placebos; Purines; Sildenafil Citrate; Sulfones; Systole - drug effects; Vasodilator Agents - blood; Vasodilator Agents - pharmacology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.105.540500

Sildenafil inhibits phosphodiesterase 5 (PDE5A) to elevate intracellular cGMP and to induce vasodilation. This effect has led to its use for treating erectile dysfunction. Although its influence on rest heart function has appeared minimal, recent animal studies suggest that sildenafil can have potent effects on hearts stimulated by beta-adrenergic or pressure overloads. We therefore tested whether sildenafil blunts dobutamine-stimulated cardiac function in humans. Thirty-five healthy volunteers underwent a randomized, double-blind, placebo-controlled study in which cardiac function was assessed in response to dobutamine before and after oral sildenafil (100 mg, n=19) or placebo (n=16). Echo Doppler and noninvasive blood pressure data yielded load-independent contractility indexes (maximal power index and end-systolic elastance), ejection fraction, and measures of diastolic function. In the initial dobutamine test, systolic and diastolic function improved similarly in both treatment groups (eg, peak power index rose 80+/-28% in the placebo group and 82+/-31% in the sildenafil group; P=NS). However, in subjects who then received sildenafil, their second dobutamine response was significantly blunted, with peak power, ejection fraction, and end-systolic elastance changes reduced by 32+/-34%, 66+/-64%, and 56+/-63%, respectively (each P