The human internal thoracic artery releases more nitric oxide in response to vascular endothelial growth factor than the human saphenous vein

Objective: Endothelial nitric oxide inhibits smooth muscle cell proliferati on, reducing the chance of vascular intimal thickening. In this study we in vestigated whether the superior long-term patency of the internal thoracic artery in human coronary bypass grafting compared with that of the saphenou s vein could be explained by different levels of nitric oxide production. Methods: The baseline endogenous nitric oxide production appeared to be 50% higher in the internal thoracic artery than in the saphenous vein. Previou sly, it was shown that vascular endothelial growth factor and the vascular endothelial growth factor receptors KDR (Flk-1) and Flt-1 are expressed in both internal thoracic arteries and saphenous veins and that vascular endot helial growth factor receptor density was higher in internal thoracic arter ies than in saphenous veins. Therefore, we also investigated the influence of vascular endothelial growth factor on nitric oxide release in both the i nternal thoracic artery and the saphenous vein. Results: Vascular endothelial growth factor augmented nitric oxide producti on by approximately 50% in the saphenous vein and 100% in the internal thor acic artery. As shown by means of immunohistochemistry, expression of endot helial constitutive nitric oxide synthase was similar in the internal thora cic artery and the saphenous vein, and no inducible nitric oxide synthase w as expressed in any of the vascular segments. Conclusion: Vascular endothelial growth factor augments endothelial constit utive nitric oxide synthase-dependent nitric oxide release to a greater ext ent in the internal thoracic artery than in the saphenous vein. These findi ngs may help to explain the long-term superiority of the internal thoracic artery versus the saphenous vein as a conduit for coronary artery bypass.