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 degrees 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 15 min of equilibration, 1 microM sildenafil was added to the bath, followed 15 min later (human and dog) by 5 microM epinephrine, an inotropic agent, and 10 min later (dog) by 88 microM 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 microM 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.
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 degrees 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 15 min of equilibration, 1 microM sildenafil was added to the bath, followed 15 min later (human and dog) by 5 microM epinephrine, an inotropic agent, and 10 min later (dog) by 88 microM 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 microM 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.
Authors: Anastacia M Garcia; Stephanie J Nakano; Anis Karimpour-Fard; Karin Nunley; Penny Blain-Nelson; Natalie M Stafford; Brian L Stauffer; Carmen C Sucharov; Shelley D Miyamoto Journal: Circ Heart Fail Date: 2018-09 Impact factor: 8.790
Authors: Manling Zhang; Norimichi Koitabashi; Takahiro Nagayama; Ryan Rambaran; Ning Feng; Eiki Takimoto; Trisha Koenke; Brian O'Rourke; Hunter C Champion; Michael T Crow; David A Kass Journal: Cell Signal Date: 2008-08-26 Impact factor: 4.315