EVIDENCE FOR PROTEIN-KINASE-C INVOLVEMENT IN ARTERIOLAR MYOGENIC REACTIVITY
EVIDENCE FOR PROTEIN-KINASE-C INVOLVEMENT IN ARTERIOLAR MYOGENIC REACTIVITY
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DOI：
10.1152/ajpheart.1990.259.5.h1586
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发表时间：
1990-11-01
影响因子：
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通讯作者：
MEININGER, GA
中科院分区：
文献类型：
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作者：
HILL, MA;FALCONE, JC;MEININGER, GA
小动脉的肌源性收缩反应与血管内压力的急剧升高相联系的细胞事件的信息很少。本研究的目的是检查是否蛋白激酶C（PKC）已牵连在收缩反应激动剂，有助于肌源性血管收缩的提睾肌小动脉。研究是在封闭在密封的有机玻璃盒中的麻醉大鼠上进行的，其中将提睾肌外置到含有克雷布溶液的浴中。增加箱内压力，使血管内压力升高20 mmHg。为了检查PKC参与，在不存在或存在PKC抑制剂的情况下进行研究：H 7（10（-9）-10（-5）M）或staurosporine（10（-10）-10（-7）M）。将抑制剂加入组织浴中，未产生可观察到的全身效应或小动脉直径变化。三级小动脉（16 +/- 1 μ m直径）对这些药物的反应和血管内压力的变化通过体内显微镜进行监测，并用视频卡尺测量血管直径。H7对肌源性血管收缩产生浓度依赖性抑制作用，在10（-5）M时，收缩程度抑制75%。类似地，星形孢菌素引起对压力诱导的收缩的浓度依赖性抑制。在10（-7）M星形孢菌素时，生肌反应被抑制82%。PKC活性的刺激剂吲哚内酰胺（10（-6）M）可诱导一级小动脉的生肌反应性，在基础条件下，一级小动脉对血管内压力升高表现出被动扩张，这一观察结果进一步支持了PKC在生肌反应中的作用。这些数据表明PKC介导的途径在调节小动脉对血管内压力增加的肌源性反应中的作用。
Little information exists as to the cellular events that couple the myogenic contractile response of an arteriole to an acute rise in intravascular presure. The aim of this study was to examine whether protein kinase C (PKC) which has been implicated in the contractile response to agonists, contributes to myogenic vasoconstriction of cremaster muscle arterioles. Studies were performed on anesthetized rats, enclosed in an airtight Plexiglas box, with the cremaster exteriorized into a bath containing Kreb's solution. Pressure in the box was increased to elevate intravascular pressure by 20 mmHg. To examine PKC involvement, studies were performed in the absence or presence of inhibitors of PKC: H 7 (10(-9)-10(-5) M) or staurosporine (10(-10)-10(-7) M). Inhibitors were added to the tissue bath and produced no observable systemic effects or alterations in arteriolar diameter. Third-order arteriole (16 +/- 1-mu-m diam) responses to these agents and alterations in intravascular pressure were monitored by in vivo microscopy and vessel diameter was measured with a video caliper. H 7 produced a concentration-dependent inhibition of myogenic vasoconstriction, inhibiting the extent of constriction by 75% at 10(-5) M. Similarly, staurosporine caused a concentration-dependent inhibition of pressure-induced constriction. At 10(-7) M staurosporine the myogenic response was inhibited by 82%. Further support for a role for PKC in the myogenic response was provided by the observation that indolactam (10(-6) M), a stimulator of PKC activity, induced myogenic reactivity in first-order arterioles, which under basal conditions show passive distension to increased intravascular pressure. These data suggest a role for PKC-mediated pathways in modulating the myogenic response of arterioles to increased intravascular pressure.