Shirinsky V P, Sobolevsky A V, Danilov S M, Tararak E M, Tkachuk V A
National Cardiology Research Center, USSR Academy of Medical Sciences, Moscow.
Health Psychol. 1988;7 Suppl:61-74. doi: 10.1037/h0090271.
Human aortic endothelial cells and smooth cells (SMC) from human aorta and coronary arteries were grown in culture. Subcultured vascular SMC retained several important features of human vascular SMC in situ, for example, vimentin-type intermediate filaments, smooth muscle myosin, a well-developed microfilament system, and expression of caldesmon protein involved in the regulation of contraction in smooth muscle. Aortic endothelial cells were shown to possess functional receptors to histamine, thrombin, serotonin, acetylcholine, bradykinin, platelet activating factor (PAF), angiotensin II, vasopressin, prostaglandin E2 (PGE2), and U46619, a stable analog of thromboxane A2. All these substances stimulated polyphosphoinositide (PPI) breakdown in endothelium. Thrombin, histamine, and PAF were the most potent activators. The response of aortic SMC to the same panel of agonists were different. Serotonin, histamine, and angiotensin II produced higher levels of inositol phosphates (IP, IP2, IP3) in SMC than in endothelium. Responses to acetylcholine, bradykinin, and PGE2 were weak and inferior to those of endothelial cells. Other agents evoked approximately equivalent responses in both cell types. Coronary artery SMC resembled aortic SMC in the high extent of PPI hydrolysis after stimulation with serotonin and histamine. The complete inability of angiotensin II and vasopressin to cause accumulation of inositol phosphates in coronary SMC contrasted with the presence of functional receptors to these hormones on aortic SMC. We conclude that the effect of vasoactive agents on human vascular cells may be realized via activation of PPI hydrolysis. Agonists with reported strong vasoconstrictor action seem to stimulate preferential PPI hydrolysis in SMC, whereas endothelium-dependent relaxers cause more pronounced PPI breakdown in endothelial cells. Peculiarities of angiotensin II and vasopressin receptor expression and/or coupling in human aorta and coronary artery SMC may be relevant for understanding the selective action of agonists on human vessels.
人主动脉内皮细胞以及来自人主动脉和冠状动脉的平滑肌细胞（SMC）在培养条件下生长。传代培养的血管平滑肌细胞保留了人血管平滑肌细胞在原位的几个重要特征，例如波形蛋白型中间丝、平滑肌肌球蛋白、发育良好的微丝系统以及参与平滑肌收缩调节的钙调蛋白的表达。已证明主动脉内皮细胞具有对组胺、凝血酶、5-羟色胺、乙酰胆碱、缓激肽、血小板活化因子（PAF）、血管紧张素II、血管加压素、前列腺素E2（PGE2）以及血栓素A2的稳定类似物U46619的功能性受体。所有这些物质均刺激内皮细胞中的多磷酸肌醇（PPI）分解。凝血酶、组胺和PAF是最有效的激活剂。主动脉平滑肌细胞对同一组激动剂的反应则不同。5-羟色胺、组胺和血管紧张素II在平滑肌细胞中产生的肌醇磷酸（IP、IP2、IP3）水平高于在内皮细胞中产生的水平。对乙酰胆碱、缓激肽和PGE2的反应较弱，且不如内皮细胞的反应。其他试剂在两种细胞类型中引起的反应大致相当。在用5-羟色胺和组胺刺激后，冠状动脉平滑肌细胞在PPI水解程度上与主动脉平滑肌细胞相似。血管紧张素II和血管加压素完全无法在冠状动脉平滑肌细胞中引起肌醇磷酸的积累，这与主动脉平滑肌细胞上存在这些激素的功能性受体形成对比。我们得出结论，血管活性药物对人血管细胞的作用可能通过激活PPI水解来实现。据报道具有强烈血管收缩作用的激动剂似乎优先刺激平滑肌细胞中的PPI水解，而内皮依赖性舒张剂在内皮细胞中引起更明显的PPI分解。血管紧张素II和血管加压素受体在人主动脉和冠状动脉平滑肌细胞中的表达和/或偶联特性可能与理解激动剂对人体血管的选择性作用有关。
