Steinhorn R H, Morin F C, Van Wylen D G, Gugino S F, Giese E C, Russell J A
Department of Pediatrics, State University of New York, Buffalo 14214.
Am J Physiol. 1994 May;266(5 Pt 2):H2001-6. doi: 10.1152/ajpheart.1994.266.5.H2001.
We studied the actions of adenosine and its analogues 5'-(N-ethylcarboxamido)-adenosine (NECA) and N6-cyclohexyladenosine (CHA) in pulmonary vessels isolated from juvenile rabbits. Pulmonary arteries relaxed in a concentration-dependent fashion to all three compounds. Pretreatment with the methylxanthine 8-p-sulfophenyltheophylline shifted the concentration-response curves to adenosine and NECA rightward, indicating that the vasodilator effects were mediated by the adenosine receptor. The order of potency of adenosine compounds was NECA > adenosine > CHA, indicating that the A2-receptor mediates relaxations to adenosine in rabbit pulmonary arteries. Endothelium rubbing attenuated relaxations to adenosine at concentrations of < or = 3 x 10(-7) M and to all NECA concentrations. Inhibition of nitric oxide synthase with NG-nitro-L-arginine (L-NNA) similarly attenuated relaxations at concentrations of < or = 3 x 10(-7) M for adenosine and < or = 3 x 10(-8) M for NECA. With the use of the same methods, a substantial endothelial contribution was additionally observed in pulmonary veins to the vasodilator effects of NECA. We conclude that adenosine, and the more specific A2-receptor agonist NECA, dilate pulmonary arteries and veins isolated from young rabbits via a mechanism that is partially dependent on endothelium-derived nitric oxide.
我们研究了腺苷及其类似物5'-(N-乙基甲酰胺基)-腺苷(NECA)和N6-环己基腺苷(CHA)对从幼年兔分离出的肺血管的作用。肺动脉对所有这三种化合物均呈浓度依赖性舒张。用甲基黄嘌呤8-对磺基苯茶碱预处理使腺苷和NECA的浓度-反应曲线右移,表明血管舒张作用是由腺苷受体介导的。腺苷化合物的效力顺序为NECA>腺苷>CHA,表明A2受体介导兔肺动脉对腺苷的舒张作用。内皮摩擦减弱了浓度≤3×10^(-7) M的腺苷以及所有浓度NECA引起的舒张作用。用NG-硝基-L-精氨酸(L-NNA)抑制一氧化氮合酶同样减弱了浓度≤3×10^(-7) M的腺苷和≤3×10^(-8) M的NECA引起的舒张作用。使用相同方法,还观察到肺静脉内皮对NECA的血管舒张作用有显著贡献。我们得出结论,腺苷以及更具特异性的A2受体激动剂NECA通过一种部分依赖于内皮衍生一氧化氮的机制,使从幼兔分离出的肺动脉和肺静脉舒张。