Effect of protein kinase C inhibition on hypoxic pulmonary vasoconstriction
Effect of protein kinase C inhibition on hypoxic pulmonary vasoconstriction
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DOI：
10.1152/ajplung.2001.280.5.l888
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发表时间：
2001-05-01
影响因子：
4.9
通讯作者：
Barman, SA
中科院分区：
文献类型：
--
作者：
Barman, SA
目前的研究是为了检验这样的假设：蛋白激酶 C (PKC) 抑制剂可防止缺氧期间孤立的血液灌注狗肺中发生的肺血管阻力和顺应性增加。通过血管闭塞技术测量肺血管阻力和顺应性。缺氧显着增加肺动脉阻力、肺静脉阻力和肺毛细血管压力，并通过降低微血管和大血管顺应性来降低总血管顺应性。非特异性PKC抑制剂星形孢菌素(10(-7)M)、特异性PKC阻滞剂钙磷蛋白C(10(-7)M)和特异性PKC同工酶阻滞剂Go-6976(10(-7)M)抑制缺氧对肺血管阻力和顺应性的影响。此外,PKC激活剂胸腺毒素(THX;10(-7)M)以类似于缺氧的方式增加肺血管阻力和顺应性,L型电压依赖性Ca2+通道阻滞剂硝苯地平(10(-6)M)抑制THX和缺氧的反应。这些结果表明 PKC 抑制可阻断缺氧升压反应，并且 THX 对 PKC 的药理激活模拟了缺氧肺血管收缩反应。此外，L 型电压依赖性 Ca2+ 通道阻断可以防止犬肺血管系统中缺氧和 PKC 诱导的血管收缩反应的发生。
The current study was done to test the hypothesis that protein kinase C (PKC) inhibitors prevent the increase in pulmonary vascular resistance and compliance that occurs in isolated, blood-perfused dog lungs during hypoxia. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. Hypoxia significantly increased pulmonary arterial resistance, pulmonary venous resistance, and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The nonspecific PKC inhibitor staurosporine (10(-7) M), the specific PKC blocker calphostin C (10(-7) M), and the specific PKC isozyme blocker Go-6976 (10(-7) M) inhibited the effect of hypoxia on pulmonary vascular resistance and compliance. In addition, the PKC activator thymeleatoxin (THX; 10(-7) M) increased pulmonary vascular resistance and compliance in a manner similar to that in hypoxia, and the L-type voltage-dependent Ca2+ channel blocker nifedipine (10(-6) M) inhibited the response to both THX and hypoxia. These results suggest that PKC inhibition blocks the hypoxic pressor response and that the pharmacological activation of PKC by THX mimics the hypoxic pulmonary vasoconstrictor response. In addition, L-type voltage-dependent Ca2+ channel blockade may prevent the onset of the hypoxia- and PKC-induced vasoconstrictor response in the canine pulmonary vasculature.