Karimi Gholamreza, Fatehi Zahra, Gholamnejad Zahra
Department of Pharmacodynamy and Toxicology, Pharmacy School, Mashhad, Iran.
J Pharm Pharm Sci. 2006;9(1):119-23.
Overactivation of nitric oxide and protein kinase C (PKC) pathway has been reported to play a role in the pathogenesis of vascular hyporesponsiveness of endotoxic shock. In this study we investigated the role of nitric oxide and PKC in lipopolysaccharide (LPS) mediated vascular hyporeactivity.
Contraction to phenylephrine and endothelium-dependent and independent vasodilation in the presence and absence of a nonspecific NO inhibitor (L-NAME) and potent PKC inhibitor (chelerythrine) were examined.
In LPS treated rats, contractile response of aortic rings to phenylephrine and relaxation in response to acetylcholine were reduced, but relaxation induced by sodium nitroprusside remained unchanged. The attenuation of contractile response to phenylephrine in the presence of L-NAME and chelerythrine was more pronounced in aortic ring isolated from LPS treated rats than control. L-NAME decreased acetylcholine -dependent vasodilation in both group but it was more pronounced in LPS treated rats. Chelerythrine pretreatment improved maximal relaxation to acetylcholine in aortic ring isolated from LPS treated rats.
These data indicate that the vascular hyporesponsiveness to phenylephrine and acetylcholine after treatment with LPS may be related to an enhanced NO production in the smooth muscle cells and PKC plays a role as an intracellular mediator of LPS-induce NOS activity and vascular suppression.
据报道，一氧化氮和蛋白激酶C（PKC）途径的过度激活在内毒素休克血管反应性降低的发病机制中起作用。在本研究中，我们调查了一氧化氮和PKC在脂多糖（LPS）介导的血管反应性降低中的作用。
检测在存在和不存在非特异性NO抑制剂（L-NAME）和强效PKC抑制剂（白屈菜红碱）的情况下，主动脉环对去氧肾上腺素的收缩反应以及内皮依赖性和非依赖性血管舒张。
在LPS处理的大鼠中，主动脉环对去氧肾上腺素的收缩反应以及对乙酰胆碱的舒张反应降低，但硝普钠诱导的舒张反应保持不变。在L-NAME和白屈菜红碱存在下，LPS处理大鼠分离的主动脉环对去氧肾上腺素的收缩反应减弱比对照组更明显。L-NAME降低了两组中乙酰胆碱依赖性血管舒张，但在LPS处理的大鼠中更明显。白屈菜红碱预处理改善了LPS处理大鼠分离的主动脉环对乙酰胆碱的最大舒张反应。
这些数据表明，LPS处理后血管对去氧肾上腺素和乙酰胆碱的反应性降低可能与平滑肌细胞中NO生成增加有关，并且PKC作为LPS诱导的NOS活性和血管抑制的细胞内介质发挥作用。
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