Role of Ca sensitivity in NO inhalation for pulmonary hypertension

Ca 敏感性在 NO 吸入治疗肺动脉高压中的作用

• 批准号: 12470319
• 负责人: MARUYAMA Kazuo
• 金额: $ 3.14万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470319/
• 关键词: Pulmonary hypertension; calcium; 一酸化窒素

To determine if increased Ca sensitivity is observed in pulmonary hypertension, we measured pulmonary pressure in pulmonary hypertensive rats after administration of Rho-kinase inhibitor. As pulmonary hypertensive rats, two models were used : chronic hypoxic pulmonary hypertension and monocrotaline-induced pulmonaryhypertension. We used Y-27632 as Rho-kinase inhibitor which had been used to show increased Ca sensitivity in systemic hypertension. Y-27632 reduced pulmonary artery pressure in both model of pulmonary hypertension, while saline did not reduced pulmonary artery pressure. This results suggested that increased Ca sensitivity might be a part of pathogenesis of pulmonary hypertension. In addition, to determine if chronic administraction of Rho-kinase inhibitor might prevent the development of pulmonary hypertension and hypertensive pulmonary vascular changes, we gave Y-27632 to rats during 10days hypoxic exposure. Chronic administration of Y-27632 did not prevent the development of pulmonary hypertension and hypertensive pulmonary vascular changes. In terms of chronic effects of Rho-kinase inhibition on the development of pulmonary hypertension, we need to investigate another Rho-kinase inhibitor.

为了确定在肺动脉高压中是否观察到Ca敏感性增加，我们在给予Rho激酶抑制剂后测量了肺动脉高压大鼠的肺压。作为肺动脉高压大鼠，采用两种模型：慢性低氧性肺动脉高压和野百合碱诱导的肺动脉高压。我们使用Y-27632作为Rho激酶抑制剂，其已被用于显示在全身性高血压中增加的Ca敏感性。Y-27632降低两种肺动脉高压模型的肺动脉压，而生理盐水不降低肺动脉压。提示钙敏感性增高可能是肺动脉高压发病机制的一部分。此外，为了确定长期给予Rho激酶抑制剂是否可以防止肺动脉高压和高血压肺血管变化的发展，我们在10天的低氧暴露期间给予大鼠Y-27632。长期给予Y-27632不能预防肺动脉高压和高血压性肺血管变化的发生。就Rho激酶抑制剂对肺动脉高压发展的慢性影响而言，我们需要研究另一种Rho激酶抑制剂。

项目成果

Mitani Y. et al.: "Modulated vasodilator responses to natriuretic peptides in rats exposed to chronic hypoixa"Eur.Respir.J. 15. 400-406 (2000)

Mitani Y. 等人：“在暴露于慢性缺氧的大鼠中调节血管舒张剂对利钠肽的反应”Eur.Respir.J。

Mitani Y., Maruyama K., Sakurai M.: "Modulated vasodilator responses to natriuretic peptides in rats exposed to chronic hypoxia"Eur. Respir. J. 15. 400-406 (2000)

Mitani Y.、Maruyama K.、Sakurai M.：“在暴露于慢性缺氧的大鼠中调节血管舒张剂对利钠肽的反应”Eur。

天野 誉: "低酸素による遺伝発現プロフィール変化の解析"ICUとCCU. 24・5. 327-332 (2000)

Homare Amano：“缺氧引起的基因表达谱变化分析”ICU 和 CCU 327-332（2000）。

Mitani Y: "Vascular smooth muscle cell phenotypes in primary pulmonary hypertension"Eur.Respir.J. 17. 316-320 (2001)

Mitani Y：“原发性肺动脉高压中的血管平滑肌细胞表型”Eur.Respir.J。

丸山一男 他: "小児急性循環・呼吸不全における一酸化窒素吸入の役割"日本集中治療学会誌. 7. 179-189 (2000)

Kazuo Maruyama 等人：“吸入一氧化氮在儿科急性循环和呼吸衰竭中的作用”日本重症监护学会杂志 7. 179-189 (2000)。