肺血管EDNO及其合酶在大鼠低氧性肺动脉高压形成中的作用

本研究观察了低氧对大鼠肺组织和血管内皮一氧化氮合酶（ＮＯＳ）活性及内皮衍生一氧化氮（ＥＤＮＯ）依赖性舒张反应的影响,以及ＮＯＳ抑制剂（Ｌ－ＮＡＭＥ）对常氧和低氧大鼠肺组织和血管内皮ＮＯＳ活性及颈、肺动脉血压（ＣＡＰｓ、ｍＰＡＰ）的作用。结果表明常氧大鼠肺泡内无肌性血管内皮未见ＮＯＳ活性,其肺血管床对ＥＤＮＯ依赖性舒血管物质ＢＫ没有反应,注射Ｌ－ＮＡＭＥ后大鼠ｍＰＡＰ略有降低,ＣＡＰｓ有所升高。低氧大鼠肺泡内无肌性血管内皮显示ＮＯＳ活性,对ＢＫ的ＥＤＮＯ依赖性舒张反应呈剂量依赖性增大,注射Ｌ－ＮＡＭＥ使低氧大鼠ｍＰＡＰ显著降低（Ｐ＜０．０１）,ＣＡＰｓ显著升高（Ｐ＜０．０５）。提示肺血管ＥＤＮＯ及其合酶在维持正常成年大鼠肺循环低压低阻中的生理作用值得进一步探讨;低氧引起肺血管内皮ｅｃＮＯＳ活性增加和ＥＤＮＯ生成增多可能起到限制肺动脉压过度升高的调制作用,也可能对肺血管内皮产生毒性作用,反而促进肺动脉高压的发生和发展。     

Pharmacological characteristics of novel putative purinoceptors in vascular endothelium

Using an isolated rat aorta with intact endothelium, a functional bioassay system was created as follows: pre-contract the isolated rat aorta with intact endothelium in the presence of 0.62 micromol/l of norepinephrine, and then add acetylcholine to obtain maximal endothelium-dependent relaxation. In the addition of low concentration of adenosine, a P(1) agonist or ATP, a P(2) agonist to this system, the rat aorta smooth muscle contraction was observed. This observation could not be explained in terms of the classic P(1) and P(2) receptor properties, suggesting that there may be a novel subtype of purinoceptors in the endothelium of the rat aorta. The P(1) and P(2) agonists-induced rat aorta smooth muscle contraction could be blocked by the pretreatments of the bioassay system with a G protein (Gi/o) inhibitor, PTX, and EDNO synthesis inhibitor, L-NAME and cyclooxygenase inhibitor, indomethacine. The data strongly support that this novel purinoceptor may couple with PTX-sensitive G protein, Gi or Go, and the novel purinoceptor-mediated rat aorta smooth muscle contraction is dependent on the endogenous nitric oxide and prostaglandin synthesis. In an additional observation, pathophysiological conditions, such as hypertension, altered the characteristics of the novel receptor. Hypertension caused the novel receptor insensitive to adensone and uncoupling to PTX-sensitive G-proteins and lost of ability to initiate the receptor-mediated prostaglandin synthesis. All together, the novel putative endothelial purinoceptor may play an important role in the control of vascular tone in physiological or pathophysiological statues.