Different Involvement of Nitric Oxide in Endothelium-Dependent Relaxation of Porcine Pulmonary Artery and Vein

Abstract

We designed experiments to determine in vitro the influence of hypoxia on endothelium function in porcine pulmonary artery and vein. Rings of large isolated intralobar pulmonary arteries and veins were mounted in organ chambers for isometric tension recording. In veins and arteries with endothelium (precontracted with histamine and U 46619, respectively), hypoxia induced a transient contractile response that was significantly greater in veins. These contractile responses were fully blocked by L-nitro arginine (LNA) in arteries but only partially in veins. In pulmonary vessels without endothelium, only venous rings produced a contractile response to hypoxia; this contraction was blocked by indomethacin. In precontracted pulmonary arterial and venous rings, bradykinin (BK) induced endothelium-dependent relaxations unaffected by indomethacin. Venous relaxations were fully blocked by LNA, but arterial relaxations were only partially inhibited by the nitric oxide (NO) synthase inhibitor. In KCl (30 mM)-precontracted vessels, the endothelium-dependent relaxations were minimally affected in veins but significantly inhibited in arteries. Identical results were obtained in tissue contracted with histamine or U 46619 in presence of tetraethyl ammonium (TEA 10 mM). Hypoxia (30 mm Hg) abolished the venous relaxation but did not significantly influence the arterial relaxation. In arterial rings, the effects of KCl and LNA (or hypoxia) were additive. These results suggest that in isolated porcine pulmonary veins, endothelium-dependent relaxation to BK is exclusively dependent on NO formation. In arteries, however, NO production is partially involved. Another mechanism, possibly endothelium-dependent hyperpolarization, exists. These differences in endothelial responsiveness lead to different patterns of response to hypoxia.