Sildenafil citrate does not affect cardiac contractility in human or dog heart
- 1 January 2003
- journal article
- research article
- Published by Taylor & Francis Ltd in Current Medical Research and Opinion
- Vol. 19 (8), 747-752
- https://doi.org/10.1185/030079903125002522
Abstract
Objective: This study evaluated whether sildenafil citrate, an oral treatment for erectile dysfunction and a selective inhibitor of phosphodiesterase type 5 (PDE5) with modest vasodilating properties, affects cardiac contractility in vitro. Research design and methods: Slices of freshly obtained human (n = 2) or dog (n = 3) atrial appendage were suspended in organ baths containing Krebs—Ringer bicarbonate buffer (pH 7.4, 37°C) bubbled continuously with 95% O2 and 5% CO2, and isometric tension was recorded using a Gould physiograph. Contractions were elicited by 1-Hz electric pacing. After 15min of equilibration, 1\M sildenafil was added to the bath, followed 15min later (human and dog) by 5|iM epinephrine, an inotropic agent, and 10min later (dog) by 88|iM 3-isobutyl-1 -methylxanthine (IBMX), a nonselective PDE inhibitor. In a separate experiment, cyclic guanosine monophosphate levels and PDE, protein kinase G, and protein kinase A activities were determined. Results: Addition of 1 |iM sildenafil to isolated dog or human atrial tissue had no significant effect on force of cardiac contraction, whereas epinephrine produced a robust increase in contractile force in the same muscle strip. The addition of IBMX produced a marked stimulation of contractile force in dog atrial tissue. Very low amounts of PDE5 were found in extracts of human heart, consistent with its known primary location in the smooth muscle of systemic vasculature. Conclusions: Sildenafil is unlikely to directly produce inotropic effects on cardiac muscle in patients being treated for erectile dysfunction.Keywords
This publication has 28 references indexed in Scilit:
- Cardiac phosphodiesterase 5 (cGMP‐specific) modulates β‐adrenergic signaling in vivo and is down‐regulated in heart failureThe FASEB Journal, 2001
- Allosteric sites of phosphodiesterase‐5 (PDE5)JBIC Journal of Biological Inorganic Chemistry, 2001
- Effect of sildenafil citrate on blood pressure and heart rate in men with erectile dysfunction taking concomitant antihypertensive medicationJournal of Hypertension, 2000
- Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton consensus panelThe American Journal of Cardiology, 2000
- Hemodynamic Effects of Sildenafil in Men with Severe Coronary Artery DiseaseThe New England Journal of Medicine, 2000
- Effects of sildenafil on cAMP and cGMP levels in isolated human cavernous and cardiac tissueUrology, 2000
- Use of Sildenafil (Viagra) in Patients With Cardiovascular DiseaseCirculation, 1999
- EFFECTS OF SILDENAFIL ON THE RELAXATION OF HUMAN CORPUS CAVERNOSUM TISSUE IN VITRO AND ON THE ACTIVITIES OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE ISOZYMESJournal of Urology, 1998
- Does severity of ischemic coronary disease correlate with erectile function?International Journal of Impotence Research, 1997
- [7] Purification and assay of cAMP, cGMP, and cyclic nucleotide analogs in cells treated with cyclic nucleotide analogsMethods in Enzymology, 1988