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

内源性一氧化氮在正常和肺动脉高压动物肺微血管张力调节中的作用

• 批准号: 07670074
• 负责人: SHIRAI Mikiyasu
• 金额: $ 0.83万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670074/
• 关键词: endogenous nitric oxide; exogenous inhaled nitric oxide; nitric oxide synthase inhibitor; pulmonary microcirculation; pulmonary hypertension; hypoxic pulmonary vasoconstriction; monocrotaline; vascular internal diameter; 急性肺高血圧; 慢性肺高血圧; 肺胞性低酸素 /

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

本研究旨在探讨内源性一氧化氮（NO）在基础状态和高血压状态下对肺血管张力的调节作用。为此，我们直接测量了小肌肉肺动脉和静脉对NO合成抑制的内径反应（100-1000 μ m ID）。在含氧量正常的猫肺中，N-硝基-L-精氨酸甲酯（L-NAME）减少了观察到的所有血管的ID，特别是200-700 μ m动脉，但L-刀豆氨酸没有导致身份改变ID减少不受神经节阻滞的影响。这些数据表明，内皮组成型NO合酶（cNOS）的连续基础NO产生有助于调节小肺动脉和静脉，特别是200-700动脉的基础血管张力。外源性吸入NO最强烈地增加了约200 - 700 μ m动脉的ID，表明这些血管对NO最敏感。 ...更多信息 NO对基础内径的影响是β-肾上腺素能、胆碱能或肾上腺素介导的扩张效应的两倍或两倍以上。这表明一个非常重要的作用，NO在维持低的基础肺血管tone.In猫肺暴露于急性缺氧，L-NAME增强缺氧ID减少在100-700 μ m的动脉和静脉，这表明，NO作为一种抑制剂急性缺氧性肺血管收缩。在缺氧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。在较小的动脉（100-300 μ m）中观察到增强的ID减小，但在较大的动脉（>300 μ m）中没有观察到增强的ID减小。L-刀豆氨酸降低了缺氧大鼠的ID，但在对照大鼠中没有。小动脉的内径减小大于大动脉。这些数据表明，诱导型一氧化氮合酶（iNOS），而不是cNOS抑制血管收缩的小动脉慢性缺氧肺动脉高压的发展过程中产生的NO。少

项目成果

Shirai, M., Shimouchi, A., and Ninomiya, I.: "Vasodilator actions of endogenous and exogenous nitric oxide in small pulmonary arteries and veins in anesthetized cats" Jpn. J.Physiol.45. S65 (1995)

Shirai, M.、Shimouchi, A. 和 Ninomiya, I.：“内源性和外源性一氧化氮对麻醉猫小肺动脉和静脉的血管扩张作用”Jpn。

Shirai, M.Shimouchi, A., Kawaguchi, A.T., Ikeda, S., Sunagawa, K., and Ninomiya, I.: "Endogenous nitric oxide attenuates hypoxic vasconstriction of small pulmonary arteries and veins in anaesthetized cats" Acta Physiol. Scand.(in press.).

Shirai, M.Shimouchi, A.、Kawaguchi, A.T.、Ikeda, S.、Sunakawa, K. 和 Ninomiya, I.：“内源性一氧化氮减轻麻醉猫小肺动脉和静脉的缺氧血管收缩”Acta Physiol。

shirai,M.: "Inhaled nitric oxide : diameter response patterns in feline small pulmonary arteries and veins" American Journal of Physiology. 270. H974-H980 (1996)

shirai,M.：“吸入一氧化氮：猫小肺动脉和静脉的直径反应模式”美国生理学杂志。

Shirai,M.: "Endogenous nitric oxicle atlenuates hypoxic vasoconstriction of small pulmenary arteries and veins in anaestheized cats" Acta Physiologica Scandinavica. In press. (1997)

Shirai,M.：“内源性一氧化氮减轻麻醉猫小肺动脉和静脉的缺氧血管收缩”《斯堪的纳维亚生理学报》。

Shirai, M.Shimouchi, A., Kawaguchi, A.T., Sunagawa, K., and Ninomiya, I.: "Inhaled nitric oxide : diameter response patterns in feline small pulmonary arteries and veins" Am. J.Physiol.270. H974-H980 (1996)

白井，M.Shimouchi，A.，川口，A.T.，砂川，K.，和二宫，I.：“吸入一氧化氮：猫小肺动脉和静脉的直径反应模式”Am。