A Study of Endothelium-dependent Pulmonary Arterial Relaxation and the Role of Nitric oxide on Acute Hypoxic Pulmonary Vasoconstriction in Rats

Abstract

Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of -monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at . Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, ) was relaxed completely by acetylcholine(Ach, ) and sodium nitroprusside(SN, ), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA() pretreatment inhibited Ach()-induced relaxation, but L-NMMA () had no effect on relaxation induced by SN(). 3) Pretreatment of the L-arginine() significantly reversed the inhibition of the Ach ()-induced relaxation caused by L-NMMA() 4) Pulmonary arterial contraction by PE() was stronger in hypoxia than normoxia but relaxing response by Ach() was decreased, 5) With pretreatment of L-arginine(), pulmonary arterial relaxation by Ach() in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.