Lagaud G J, Skarsgard P L, Laher I, van Breemen C
Vancouver Vascular Biology Research Centre, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
J Pharmacol Exp Ther. 1999 Aug;290(2):832-9.
We compared endothelial responses to calcium-mobilizing agents in mesenteric and cerebral resistance arteries of the rat. Middle cerebral and small mesenteric arteries were mounted in a pressure myograph, and myogenic responses were recorded. The effects of acetylcholine (ACh), bradykinin, substance P, histamine, A23187, cyclopiazonic acid (CPA), and sodium nitroprusside were investigated in both arteries with myogenic tone in the absence and presence of nitric oxide synthase and cyclooxygenase inhibitors. The effects of raised potassium, K(+) channel blockers, and arachidonic metabolism inhibition were examined on the nitric oxide (NO) synthase/cyclooxygenase inhibitor-resistant dilation induced by ACh and CPA. Cerebral arteries display a high level of myogenic reactivity compared with mesenteric arteries. In cerebral arteries, only bradykinin and substance P induced endothelium-dependent dilation. The observed dilation was solely related to the activation of the NO pathway. However, in mesenteric arteries, all of the vasoactive agents induced endothelium-dependent dilation. A combination of NO, cyclooxygenase-derived prostanoids, and a factor with endothelium-derived hyperpolarizing factor-like properties was responsible for the observed vasodilation. NO and cyclooxygenase derivatives were able to compensate for each other in the CPA-induced endothelium-dependent vasodilation when one of the two pathways was blocked. Moreover, small Ca(2+)-activated K(+) channels and a combination of both large and small Ca(2+)-activated K(+) channels were implicated in the endothelium-derived hyperpolarizing factor-like component of dilation to ACh and CPA, respectively. Finally, the results suggest that the pathway by which agonists raise intracellular calcium concentration may determine the nature of the endothelial secretory product.
我们比较了大鼠肠系膜和脑阻力动脉对钙动员剂的内皮反应。将大脑中动脉和肠系膜小动脉安装在压力肌动描记器中，并记录肌源性反应。在一氧化氮合酶和环氧化酶抑制剂存在和不存在的情况下，研究了乙酰胆碱（ACh）、缓激肽、P物质、组胺、A23187、环匹阿尼酸（CPA）和硝普钠对两条具有肌源性张力动脉的影响。研究了钾升高、钾（K+）通道阻滞剂和花生四烯酸代谢抑制对ACh和CPA诱导的一氧化氮（NO）合酶/环氧化酶抑制剂抗性扩张的影响。与肠系膜动脉相比，脑动脉表现出高水平的肌源性反应性。在脑动脉中，只有缓激肽和P物质诱导内皮依赖性扩张。观察到的扩张仅与NO途径的激活有关。然而，在肠系膜动脉中，所有血管活性药物均诱导内皮依赖性扩张。NO、环氧化酶衍生的前列腺素和具有内皮衍生超极化因子样特性的因子共同导致了观察到的血管舒张。当两条途径之一被阻断时，NO和环氧化酶衍生物能够在CPA诱导的内皮依赖性血管舒张中相互补偿。此外，小的钙激活钾（Ca2+）通道以及大、小钙激活钾通道的组合分别参与了对ACh和CPA舒张的内皮衍生超极化因子样成分。最后，结果表明激动剂升高细胞内钙浓度的途径可能决定内皮分泌产物的性质。
