Influence of Zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed.
Influence of Zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed.
复制标题
扎普司特对猫肺血管床血管张力和血管舒张反应的影响。
DOI：
10.1152/jappl.1993.74.4.1704
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Kadowitz,PJ
中科院分区：
文献类型：
--
作者：
McMahon,TJ;Ignarro,LJ;Kadowitz,PJ
研究了鸟苷3′，5′-环单磷酸（cGMP）特异性磷酸二酯酶抑制剂Zaprinast （M&B 22948）在控制血流和恒定左心房压条件下对猫肺血管床的影响。在基线条件下，将Zaprinast注射到灌注的大叶动脉中，使大叶动脉压小幅下降，而不改变全身动脉压或左心房压。当使用U-46619增加张力时，Zaprinast引起大剂量依赖性的叶动脉压下降，但不改变左心房压。用一氧化氮（NO）合成抑制剂ng -硝基- l -精氨酸甲酯（L-NAME）或鸟苷酸环化酶抑制剂亚甲基蓝治疗可显著降低大鼠叶动脉压。在张力升高的情况下，输出迷走神经刺激和叶内注射乙酰胆碱、P物质、NO溶液和s -亚硝基硫醇[s -亚硝基-n -乙酰青霉素胺（SNAP）和s -亚硝基- l -半胱氨酸（CysNO）]以频率依赖和剂量相关的方式降低了叶动脉压。经Zaprinast治疗后，输出迷走神经刺激、内皮依赖性血管扩张剂和硝基血管扩张剂引起的叶动脉压下降没有改变，而以半倍测量的血管扩张剂反应持续时间明显增加。血管扩张剂对腺苷、沙丁胺醇和pinacidil的反应未被Zaprinast改变。这些数据表明，cGMP在肺中的水解是快速的，内皮来源的NO在刺激cGMP的基础产生和调节血管张力方面是重要的。（摘要删节250字）
The influence of Zaprinast (M&B 22948), a guanosine 3′,5′-cyclic monophosphate (cGMP)-specific phosphodiesterase inhibitor, was investigated in the pulmonary vascular bed of the cat under conditions of controlled blood flow and constant left atrial pressure. Under baseline conditions, injections of Zaprinast into the perfused lobar artery produced small decreases in lobar arterial pressure without altering systemic arterial or left atrial pressure. When tone was increased with U-46619, Zaprinast caused larger dose-dependent decreases in lobar arterial pressure without altering left atrial pressure. The decreases in lobar arterial pressure were reduced significantly by treatment with the nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the guanylate cyclase inhibitor methylene blue. Under elevated tone conditions, efferent vagal stimulation and intralobar injections of acetylcholine, substance P, NO solution, and the S-nitrosothiols [S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-L-cysteine (CysNO)] decreased lobar arterial pressure in a frequency-dependent and dose-related manner. After treatment with Zaprinast, the decreases in lobar arterial pressure in response to efferent vagal stimulation, the endothelium-dependent vasodilators, and the nitrovasodilators were not changed, whereas the duration of the vasodilator responses as measured by the half times was increased significantly. Vasodilator responses to adenosine, albuterol, and pinacidil were not altered by Zaprinast. These data suggest that cGMP hydrolysis in the lung is rapid and that endothelium-derived NO is important in stimulating basal cGMP production and in regulating vascular tone.(ABSTRACT TRUNCATED AT 250 WORDS)