Role of Ca sensitivity in NO inhalation for pulmonary hypertension

为了确定是否在肺动脉高压中观察到Ca敏感性的增加，我们测量了给予rho激酶抑制剂后肺动脉高压大鼠的肺动脉压。以肺动脉高压大鼠为研究对象，建立了慢性低氧性肺动脉高压模型和单芥碱性肺动脉高压模型。我们使用Y-27632作为rho激酶抑制剂，该抑制剂已用于显示全体性高血压患者Ca敏感性增加。Y-27632降低了两种肺动脉高压模型的肺动脉压，而生理盐水没有降低肺动脉压。提示Ca敏感性增高可能是肺动脉高压发病机制的一部分。此外，为了确定长期给药rho激酶抑制剂是否可以预防肺动脉高压的发展和高血压性肺血管改变，我们给大鼠进行了10天的缺氧暴露。长期给药Y-27632不能预防肺动脉高压的发展和高血压性肺血管改变。至于rho激酶抑制对肺动脉高压发展的慢性影响，我们需要研究另一种rho激酶抑制剂。

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.