Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels

Background. Sildenafil is currently used in the treatment of erectile dysfu nction. However, assessment of direct effects of sildenafil on coronary art eries and on arteries used as coronary grafts is unknown. This study was de signed to investigate the effects of sildenafil on contracted human coronar y, internal mammary, and radial arteries obtained from multiorgan donors. T he observations were extended to forearm veins. Zaprinast was included in t his study for comparison. Methods. Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings w ere suspended in organ bath chambers and isometric tension was recorded. Th en the effects of sildenafil, zaprinast, and sodium nitroprusside on precon tracted vessels were studied. Results. Sildenafil (10(-8) - 3 x 10(-5) mol/L) caused concentration-depend ent relaxation in the internal mammary arteries, radial arteries, and forea rm veins. In the coronary arteries, sildenafil had a modest relaxant effect . In addition, sildenafil amplified the relaxation induced by sodium nitrop russide in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase N-G-monomethyl-L-arginine (10(-4) mol/L). Compared wi th zaprinast, sildenafil was eight to ten times more potent in terms of EC5 0 values. Conclusions. The direct relaxant effects of sildenafil together with its sy nergistic interaction with nitric oxide donors should be considered in pati ents undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes. (C) 2000 by The Society of Thoracic Surgeons.