Effects of sildenafil (viagra) on human myocardial contractility, in vitro arrhythmias, and tension of internal mammaria arteries and saphenous veins.
Sildenafil (Viagra) has been proved effective in the therapy for erectile dysfunction. Cardiovascular adverse effects are a matter of continuous debate. The aim of the study was to investigate effects of sildenafil on isolated human cardiovascular tissue directly. Isometric force of contraction was determined in isolated, electrically stimulated (1 Hz, 37 degrees C) human right atrial and left ventricular muscle strips. Vascular tension was determined in rings of human internal mammaria arteries and saphenous veins. Sildenafil (0.0001-10 microM) neither in human atrium (n = 12) nor in failing (n = 8) or nonfailing (n = 5) ventricle exerted a significant inotropic response. Furthermore, no effect on isoprenaline-elicited arrhythmias was observed. Neither addition of isoprenaline (0.1 microM) nor addition of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) (100 microM) affected myocardial contractility in the presence of sildenafil (10 microM). In precontracted arteries and veins, addition of sildenafil (0.1-10 microM) led to pronounced vasorelaxation (maximal 35.5 +/- 2.2% and 45.6 +/- 6.3%, respectively, in the presence of 10 microM sildenafil). In the presence of SNAP (0.03 microM), this effect was markedly increased in arteries (72.4 +/- 10.1%, n = 4, P < 0.02) as well as in veins (73.5 +/- 6.3%, n = 6, P < 0.02). Sildenafil exerts potent vasodilatory actions but has no direct influence on human myocardial contractility or proarrhythmic effects in vitro.
Cremers
Bodo
B
Medizinische Klinik und Poliklinik, Innere Medizin III, Chirurgische Klinik und Poliklinik, Abteilung Thorax-und Herz-, Homburg, Germany,
Scheler
Marina
M
Maack
Christoph
C
Wendler
Olaf
O
Schäfers
Hans-Joachim
HJ
Südkamp
Michael
M
Böhm
Michael
M
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004558:Electric Stimulation; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D020105:Milrinone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D011687:Purines; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D000068677:Sildenafil Citrate; D013450:Sulfones; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D026423:S-Nitroso-N-Acetylpenicillamine; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D020105:Milrinone; D007545:Isoproterenol