Sildenafil Inhibits β-Adrenergic–Stimulated Cardiac Contractility in Humans
- 25 October 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 112 (17), 2642-2649
- https://doi.org/10.1161/circulationaha.105.540500
Abstract
Background— 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 β-adrenergic or pressure overloads. We therefore tested whether sildenafil blunts dobutamine-stimulated cardiac function in humans. Methods and Results— 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 Conclusions— PDE5A inhibition by sildenafil blunts systolic responses to β-adrenergic stimulation. This finding supports activity of PDE5A in the human heart and its role in modifying stimulated cardiac function.Keywords
This publication has 34 references indexed in Scilit:
- Sildenafil: Emerging Cardiovascular IndicationsThe Annals of Thoracic Surgery, 2004
- Treatment of Pulmonary Arterial HypertensionNew England Journal of Medicine, 2004
- Cyclic GMP-Dependent Protein Kinases and the Cardiovascular SystemCirculation Research, 2003
- Long-Term Treatment With Oral Sildenafil Is Safe and Improves Functional Capacity and Hemodynamics in Patients With Pulmonary Arterial HypertensionCirculation, 2003
- PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in SmokersHypertension, 2003
- Sildenafil citrate does not affect cardiac contractility in human or dog heartCurrent Medical Research and Opinion, 2003
- Interaction of Sildenafil With cAMP-Mediated Vasodilation In VivoHypertension, 2002
- Sildenafil Effects on Exercise, Neurohormonal Activation, and Erectile Dysfunction in Congestive Heart FailureCirculation, 2002
- Cardiac phosphodiesterase 5 (cGMP‐specific) modulates β‐adrenergic signaling in vivo and is down‐regulated in heart failureThe FASEB Journal, 2001
- cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes.JCI Insight, 1997