Protein kinase C-mediated pulmonary vasoconstriction in rabbit: role of Ca2+, AA metabolites, and vasodilators.
Protein kinase C-mediated pulmonary vasoconstriction in rabbit: role of Ca2+, AA metabolites, and vasodilators.
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蛋白激酶 C 介导的兔肺血管收缩：Ca2、AA 代谢物和血管扩张剂的作用。
DOI：
10.1152/jappl.1993.74.3.1310
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Gurtner,GH
中科院分区：
文献类型：
--
作者：
Michael,JR;Yang,J;Farrukh,IS;Gurtner,GH
We studied the effects of three chemically distinct protein kinase C activators on pulmonary vascular tone in the buffer-perfused isolated rabbit lung. The three activators, 12-deoxyphorbol 13-isobutyrate (12,13-phorbol), mezerein, and 1-oleoyl-2-acetyl-sn-glycerol, produce concentration-dependent increases in pulmonary arterial pressure, whereas the inactive compound 4 alpha-phorbol 12,13-dibutyrate does not affect pulmonary arterial pressure. Reducing calcium availability with verapamil, a calcium-free buffer, or a chelator of intracellular calcium significantly decreases the response to 12,13-phorbol or mezerein. Pretreatment with phloretin, an inhibitor of protein kinase C, has no affect on the vasoconstriction caused by infusion of a KCl bolus, but it does inhibit in a dose-dependent manner the response to 12,13-phorbol and mezerein. 12,13-Phorbol at a concentration of 2.5 microM, but not of 1 microM, stimulates prostacyclin and thromboxane synthesis by the isolated lung. Because inhibitors of thromboxane synthesis significantly decrease the response, thromboxane likely contributes to the vasoconstriction produced by higher concentrations of 12,13-phorbol and mezerein. Pretreatment with isoproterenol or nitroprusside reduces the increase in pulmonary arterial pressure caused by the protein kinase C activators but does not reverse vasoconstriction, even though subsequent treatment with verapamil does. In summary, activating protein kinase C in the isolated rabbit lung causes long-lasting pulmonary vasoconstriction, reducing calcium availability decreases the response, part of the increase in pulmonary arterial pressure appears secondary to thromboxane generation, and pretreatment with isoproterenol or nitroprusside prevents the vasoconstriction, but posttreatment with these vasodilators is ineffective.
