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Ann Thorac Surg 2000;70:1327-1331
© 2000 The Society of Thoracic Surgeons

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Original articles: cardiovascular

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

^a Department of Physiology, University of Valencia, Valencia, Spain
^b Department of Surgery, University of Valencia, Valencia, Spain

Address reprint requests to Dr Lluch, Department of Physiology, Facultad de Medicina y Odontología, Avda Blasco Ibáñez 17, 46010 Valencia, Spain
e-mail: medinap{at}post.uv.es

Background. Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison.

Methods. Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was recorded. Then the effects of sildenafil, zaprinast, and sodium nitroprusside on precontracted vessels were studied.

Results. Sildenafil (10^-8 - 3 x 10^-5 mol/L) caused concentration-dependent relaxation in the internal mammary arteries, radial arteries, and forearm veins. In the coronary arteries, sildenafil had a modest relaxant effect. In addition, sildenafil amplified the relaxation induced by sodium nitroprusside in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase N^G-monomethyl-L-arginine (10^-4 mol/L). Compared with zaprinast, sildenafil was eight to ten times more potent in terms of EC₅₀ values.

Conclusions. The direct relaxant effects of sildenafil together with its synergistic interaction with nitric oxide donors should be considered in patients undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes.

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