Segmental differences in the mechanism of vascular tone regulation along the serially-connected pulmonary vessels in vivo

体内串联肺血管血管张力调节机制的节段差异

• 批准号: 10670056
• 负责人: SHIRAI Mikiyasu
• 金额: $ 1.34万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670056/
• 关键词: pulmonary circulation; hypoxic pulmonary vasoconstriction; muscular pulmonary arteries; elastic pulmonary arteries; nitric oxide synthase; K^+ channel; chronic hypoxic pulmonary hypertension; microcirculation; 免疫組織化学; 血管口径; ラット; 肺小葉; 肺細葉; 肺小血

This study was conducted to investigate segmental differences in the mechanism of vascular tone regulation along the in vivo serially-connected pulmonary vessels, from conduit to resistance segments. To this end, we directly measured effects of inhibitors of nitric oxide synthase (NOS) and K^+ channel on the internal diameter (ID) of resistance arteries (RA) and conduit arteries (CA), using an X-ray television system on anesthetized cats and rats. Moreover, immunohistochemistry analysis for NOS protein was also conducted.Acute hypoxic exposure-induced ID constriction (HPV) was localized in intralobular 100-600μm vessels in the cat, the maximum response being in 200-300μm RA.This response pattern was specific for hypoxia, since inhalations of nitric oxide (NO) and prostacyclin caused ID responses in pulmonary vessels with a more extensive ID range (100-1000μm).In normoxic cats, non-selective NOS inhibition caused a larger ID constriction in CA than in RA.During hypoxic exposure, the inh … More ibition enhanced HPV within the lobule. Voltage-dependent K^+ (K_v) channel inhibition caused almost uniform ID constriction in both CA and RA during normoxia, but Ca^<2+>-sensitive K^+ (K_<Ca>) channel or ATP-sensitive K^+ (K_<ATP>) channel inhibition caused a great constriction in CA and a slight constriction in RA.Under K_<Ca> channel inhibition, hypoxia induced a significant ID constriction also in smaller CA and HPV in RA was slightly enhanced. K_<ATP> channel inhibition had no effect on any of the hypoxic responses. The results suggest that K_V channels regulate basal tone in all arteries, whereas NOS and K_<Ca> and K_<ATP> channels chiefly regulate CA.The data also suggest that HPV in RA is almost independent of K_<Ca> and K_<ATP> channels, whereas the hypoxic CA response depends on the balance between the hypoxia-induced constriction and K_<Ca> channel-mediated dilatation.In rats with 4-wk hypoxic exposure, the ID constriction due to nonselective NOS inhibition was enhanced in RA, but not in CA.The enhancement was observed in all branches of RA.The ID constriction due to iNOS selective inhibition was enhanced only in 〜50% of RA.nNOS selective inhibition had no effect. The percentage of eNOS-positive RA increased to 95% (from 50%) in response to 4-wk hypoxia, but that for iNOS only to 50% (from 10%). The data suggest that eNOS mediated basal tone regulation is enhanced in all RA during chronic hypoxia, but that for iNOS sporadically among their branches. Such NOS upregulation may contribute to attenuating HPV and in turn, inhibit the pulmonary hypertension progress.Together, it is suggested that NOS- and K^+ channel-mediated mechanisms of vascular tone regulation significantly differ between the HPV-positive RA and HPV-negative CA. Less

本研究旨在探讨在体肺血管从导管段到阻力段的血管张力调节机制的节段性差异，这些血管沿着串联连接的肺血管。为此，我们在麻醉的猫和大鼠上，使用X射线电视系统直接测量了一氧化氮合酶（NOS）和K^+通道抑制剂对阻力动脉（RA）和导管动脉（CA）内径（ID）的影响。急性缺氧诱导的ID收缩（HPV）在猫的小叶内100-600μm的血管中有表达，在200-300μm的RA中有最大的反应，这种反应模式是缺氧特异性的，由于吸入一氧化氮（NO）和前列环素引起肺血管ID反应，在常氧条件下，非选择性NOS抑制引起CA的ID收缩大于RA。 ...更多信息 吸吮增强了小叶内的HPV。电压依赖性K^+（K_v）通道抑制可使CA和RA的ID在常氧条件下几乎一致地收缩，而Ca^&lt;2+&gt;敏感性K^+（K_<Ca>）通道或ATP敏感性K^+（K_<ATP>）通道抑制可使CA的ID显著收缩，RA的ID轻微<Ca>收缩。K通道<ATP>抑制对上述缺氧反应无影响。结果表明，K_V通道调节所有动脉的基础张力，而NOS、K_<Ca>和K_<ATP>通道主要调节CA。RA中的HPV几乎不依赖于K_<Ca>和K_<ATP>通道，而缺氧CA反应取决于缺氧引起的收缩和K_通道介导的扩张之间的平衡<Ca>。在大鼠缺氧暴露4周后，RA中由于非选择性NOS抑制引起的ID收缩增强，而CA中则无此效应。RA的所有分支均观察到这种增强。缺氧4周后，eNOS阳性RA的百分比从50%增加到95%，而iNOS阳性RA的百分比仅从10%增加到50%。这些数据表明，eNOS介导的基础张力调节增强在所有RA慢性缺氧，但iNOS零星在其分支。这种NOS的上调可能有助于减弱HPV，进而抑制肺动脉高压的进展，这表明NOS和K^+通道介导的血管张力调节机制在HPV阳性RA和HPV阴性CA之间存在显著差异。少

项目成果

Shirai,M.: "Segmental differences in vasodilatation due to basal NO release in in vivo cat pulmonary vessels"Respiration Physiology. 116. 159-169 (1999)

Shirai,M.：“体内猫肺血管中基础 NO 释放导致血管舒张的分段差异”呼吸生理学。

Shirai,M.: "KATP channels predominantly regulate conduit vessel tone in normoxic cat pulmonary arteries in vivo"European Journal of Pharmacology. (in press). (2001)

Shirai,M.：“KATP 通道主要调节体内含氧量正常的猫肺动脉中的导管血管张力”《欧洲药理学杂志》。

Shirai, M., Ikeda, S., Min, K-Y, Shimouchi, A., Kawaguchi, A.T.and Ninomiya, I.: "Segmental differences in vasodilatation due to basal NO release in vivo cat pulmonary vessels."Respir. Physiol.. 116. 159-169 (1999)

Shirai, M.、Ikeda, S.、Min, K-Y、Shimouchi, A.、Kawaguchi, A.T. 和 Ninomiya, I.：“猫肺血管体内基础 NO 释放导致血管舒张的分段差异。”呼吸。

Kawaguchi,A.T.: "Afferent reinnervation after lung transplantation in the rat"Journal of Heart Lung Transplantation. 17. 341-348 (1998)

Kawaguchi, A.T.：“大鼠肺移植后的传入神经支配”心肺移植杂志。

Shirai,M.: "Segmental differences in vasodilation due to basal NO release in in vivo cat pulmonary vessels" Respiration Physiology. (In press). (1999)

Shirai,M.：“体内猫肺血管中基础 NO 释放导致血管舒张的分段差异”呼吸生理学。