MECHANISMS OF MYOGENIC ENHANCEMENT BY NOREPINEPHRINE
MECHANISMS OF MYOGENIC ENHANCEMENT BY NOREPINEPHRINE
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DOI：
10.1152/ajpheart.1994.266.2.h440
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发表时间：
1994-02-01
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：
LIU, J;HILL, MA;MEININGER, GA
在大鼠提睾肌上研究了去甲肾上腺素（NE）增强小动脉肌源性反应能力的机制。将麻醉的大鼠封闭在密封盒中，该密封盒可以加压以增加提睾肌中的血管内压力，该提睾肌外置到组织浴中。在箱压增加10、20和30 mmHg期间，测量一级（1A）小动脉的血管直径、血管内压和红细胞流速。对照小动脉[直径= 113 +/- 3（SE）μ m]对血管内压力的逐步增加没有表现出肌源性收缩（例如，+ 30 mmHg，直径= 122 +/- 5 μ m），而在NE收缩25%（直径= 85 +/- 2 μ m）后，小动脉显示出显著的肌源性收缩（例如，+30 mmHg，直径= 70 +/- 4 μ m）NE对肌源性反应性的作用被Ca 2+通道激动剂增强，并被拮抗剂抑制，这表明电压操纵的Ca 2+通道发挥作用。与NE相反，暴露于KCl（30 mM）并没有增强肌源性反应性，这表明除了电压操纵性通道之外，还有其他因素参与NE效应。发现蛋白激酶C（PKC）激活剂吲哚内酰胺（1 μ M）增加1A小动脉（直径= 109 +/- 6至89 +/- 7 μ m）中的血管张力，并诱导与NE产生的类似的显著肌源性反应（例如，+30 mmHg，直径= 65 +/- 9 μ m）。星形孢菌素（0.1 μ M）和calphostin C（1 μ M），PKC抑制剂，显着衰减NE诱导的肌源性反应。物理因素，例如，NE引起的收缩、壁张力和剪切率的程度不能解释NE增强小动脉肌源性反应的能力。结果表明，电压操纵的Ca ~（2+）通道和PKC介导的事件都在肾上腺素能促进小动脉肌源性反应中起作用。
Mechanisms contributing to the ability of norepinephrine (NE) to enhance arteriolar myogenic responsiveness were studied in the rat cremaster muscle. Anesthetized rats were enclosed in an airtight box that could be pressurized to increase intravascular pressure in the cremaster, which was exteriorized into a tissue bath. Vessel diameter, intravascular pressure, and red cell velocity were measured in the first-order (1A) arteriole during box pressure increases of 10, 20, and 30 mmHg. Control arterioles [diameter = 113 +/- 3 (SE) mu m] did not exhibit myogenic constriction in response to step increases in intravascular pressure (e.g., +30 mmHg, diameter = 122 +/- 5 mu m), whereas after 25% constriction with NE (diameter = 85 +/- 2 mu m) arterioles exhibited significant myogenic constriction (e.g., +30 mmHg, diameter = 70 +/- 4 mu m) The NE effect on myogenic reactivity was augmented by Ca2+ channel agonists and inhibited by antagonists, suggesting a role for voltage-operated Ca2+ channels. In contrast to NE, exposure to KCl (30 mM) did not enhance myogenic responsiveness, suggesting that factors in addition to voltage-operated channels were involved in the NE effect. The protein kinase C (PKC) activator indolactam (1 mu M) was found to increase vascular tone in the 1A arterioles (diameter = 109 +/- 6 to 89 +/- 7 mu m) and to induce significant myogenic responsiveness similar to that produced by NE (e.g., +30 mmHg, diameter = 65 +/- 9 mu m). Staurosporine (0.1 mu M) and calphostin C (1 mu M), inhibitors of PKC, significantly attenuated the NE-induced myogenic response. Physical factors, e.g., the extent of NE-induced constriction, wall tension, and shear rate could not explain the ability of NE to enhance arteriolar myogenic responsiveness. The results suggest that both voltage-operated Ca2+ channels and PKC-mediated events act in adrenergic facilitation of arteriolar myogenic reactivity.