Role Of endogenous nitoric oxide in regulating pulmonary microvascular tone in normal and pulmonary hypertensive animals

本研究旨在探讨内源性一氧化氮（NO）在基础和高血压条件下调节肺血管张力的作用。为此，我们使用x射线电视系统在猫或大鼠的体内肺上直接测量了内径对NO合成抑制的反应。在常氧猫肺中，n -硝基- l -精氨酸甲酯（L-NAME）降低了观察到的所有血管的ID，特别是200-700条母动脉，但l -大麻酚没有引起ID改变。神经节阻滞不影响ID降低。这些数据表明，内皮型一氧化氮合酶（cNOS）持续的基础一氧化氮生成有助于调节肺小动脉和静脉的基础血管张力，特别是200-700动脉。外源性吸入NO对-200-700 mum动脉的ID增加最为强烈，表明这些血管对NO最为敏感。内源性…More NO对基底ID的扩张作用比β -肾上腺素能、胆碱能或前列腺素介导的扩张作用大2倍或更多。这表明一氧化氮在维持低基础肺血管张力中的重要作用。在暴露于急性缺氧的猫肺中，L-NAME增强了100-700个母动脉和静脉的缺氧ID减少，表明NO可作为急性缺氧肺血管收缩的抑制剂。外源性NO可以完全消除低氧ID的减少，这一发现支持了这一观点。在暴露于缺氧2-3周的大鼠肺中，n -单甲基- l-精氨酸引起的ID降低明显大于对照组。在小动脉（100-300 mum）中观察到增强的ID降低，但在大动脉（bb0 -300 mum）中没有。l - canavine在缺氧大鼠中降低了ID，而在对照大鼠中没有。小动脉的内径降低幅度大于大动脉。这些数据表明，在慢性低氧性肺动脉高压的发展过程中，诱导NOS （iNOS）而不是cNOS产生NO抑制小动脉的血管收缩。少

This study was conducted to investigate the role of endogenous nitric oxide (NO) in regulating pulmonary vascular tone under basal and hypertensive conditions. To this end, we directly measured internal diameter responses to NO synthesis inhibition in small muscular pulmonary arteries and veins (100-1000 mum ID), using an X-ray television system on the in vivo cat or rat lung.In the normoxic cat lung, N-nitro-L-arginine methyl ester (L-NAME) reduced the ID of all vessels observed, particularly 200-700 mum arteries, but L-canavaninecaused no ID change. The ID reduction was unaffected by ganglion blockade. The data suggest that continuous basal NO production by endothelial constitutive NO synthase (cNOS) contributes to the regulation of basal vascular tone of small pulmonary arteries and veins, particularly 200-700 arteries. Exogenous inhaled NO increased the ID of -200-700 mum arteries most strongly, suggesting that these vessels are most sensitive to NO.The dilator effect of endogenous … More NO on the basal ID was about two or more times larger than the beta-adrenergic, cholinergic, or prostaglandin-mediated dilator effect. This suggests a very important role of NO in maintaining low basal pulmonary vascular tone.In the cat lung exposed to acute hypoxia, L-NAME potentiated hypoxic ID reductions in 100-700 mum arteries and veins, suggesting that NO acts as an inhibitor for acute hypoxic pulmonary vasoconstriction. This suggestion was supported by the finding that exogenous NO could completely abolish the hypoxic ID reductions.In the rat lung exposed to hypoxia for 2-3weeks, N-monomethyl-L-arginine caused significantly larger ID reductions than those for the control rat. The enhanced ID reduction was observed in smaller arteries (100-300 mum), but not in larger arteries (>300 mum). L-Canavanine reduced the ID in the hypoxic rat, but not in the control rat. The ID reduction was larger in the smaller arteries than in the larger arteries. The data suggest that NO generation by inducible NOS (iNOS) rather than cNOS inhibits vasoconstrictions of smaller arteries during the development of chronic hypoxic pulmonary hepertension. Less