cGMP and cAMP cause pulmonary vasoconstriction in the presence of hemolysate.
cGMP and cAMP cause pulmonary vasoconstriction in the presence of hemolysate.
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cGMP 和 cAMP 在溶血产物存在下引起肺血管收缩。
DOI：
10.1152/jappl.1999.86.5.1715
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Burke,TJ
中科院分区：
文献类型：
--
作者：
Voelkel,NF;Allard,JD;Anderson,SM;Burke,TJ
我们最近报道，除了少量的溶血产物灌注离体大鼠肺的盐溶液的血管过敏，随后添加血管紧张素II或暴露于缺氧，并添加NO气体（NO2-NO）的灌注液中含有溶血引起了强烈的血管收缩，而不是血管舒张反应。在本研究中，我们证明，CO和第二信使cGMP和cAMP（通常与血管舒张）发挥类似的作用，在溶血灌注肺。类似物的环核苷酸cGMP或cAMP（8-溴-cGMP和二丁酰-cAMP，分别）引起深刻的血管收缩，在离体大鼠肺灌注含有溶血产物的盐溶液。cGMP-或cAMP-类似物诱导的血管收缩被化学上不同的Ca 2+拮抗剂，蛋白磷酸酶抑制剂冈田酸，并在较小程度上，蛋白激酶抑制剂H-7抑制。抗磷酸苏氨酸免疫印迹表明，肺灌注与溶血表现出增加磷酸化的几种蛋白质。这些数据表明，在存在溶血产物的情况下，肺血管系统响应于名义上的血管舒张刺激，包括cGMP和cAMP的类似物，具有血管收缩而不是血管舒张。我们发现的重要性是对环核苷酸（类似物）的反应的矛盾性质，因为据我们所知，环核苷酸诱导的血管收缩以前没有报道过。
We recently reported that addition of a small amount of hemolysate to the salt solution that perfused isolated rat lungs hypersensitized the vasculature to subsequent additions of ANG II or exposure to hypoxia, and addition of NO gas (⋅ NO) to the perfusate that contained hemolysate caused a strong vasoconstrictor rather than a vasodilator response. In the present study, we demonstrate that CO and the secondary messengers cGMP and cAMP (usually associated with vasodilation) exert similar effects in hemolysate-perfused lungs. Analogs of the cyclic nucleotides cGMP or cAMP (8-bromo-cGMP and dibutyryl-cAMP, respectively) caused profound vasoconstriction in the isolated rat lung perfused with a salt solution that contained hemolysate. The cGMP- or cAMP-analog-induced vasoconstriction was inhibited by chemically dissimilar Ca2+antagonists, by the protein phosphatase inhibitor okadaic acid, and, to a lesser degree, by protein kinase inhibitor H-7. Antiphosphothreonine immunoblotting demonstrated that lungs perfused with hemolysate exhibit increased phosphorylation of several proteins. These data indicate that, in the presence of hemolysate, pulmonary vasculature responds to nominally vasodilatory stimuli, including analogs of cGMP and cAMP, with vasoconstriction rather than vasodilation. The importance of our finding is the paradoxical nature of the response to (analogs of) cyclic nucleotides because, to our knowledge, cyclic nucleotide-induced vasoconstriction has not been previously reported.