Ragazzi E, Chinellato A, Pandolfo L, Froldi G, Caparrotta L, Prosdocimi M, Aliev G, Fassina G
Department of Pharmacology, University of Padova, Italy.
J Pharmacol Exp Ther. 1993 Aug;266(2):1091-6.
The mechanism of the unimpaired relaxant effect of ATP in the Watanabe heritable hyperlipidemic rabbit aorta was investigated to elucidate the involvement of P2y purinoceptor at the endothelial level during atherosclerosis. Experiments were carried out on isolated thoracic aorta from such rabbits that were 12 months of age. The potent P2y purinoceptor agonist, 2-methylthio-ATP, did not induce any endothelium- or smooth muscle-dependent relaxation, thus excluding any involvement by the P2y purinoceptor. ADP, but not AMP, produced relaxation of the aorta by acting at both endothelial and smooth muscle levels. Adenosine relaxed the vessel by acting only in smooth muscle. The maintained endothelial relaxant effect of ATP and ADP is therefore not due to activation of P1 or P2y purinoceptors but may involve activation of a remodeled purinergic receptor site that emerges with the progression of atherosclerosis. This site is antagonized by methylene blue. The disorganization of the endothelial monolayer observed in the morphological analysis may be related to functional remodeling of the endothelial purinergic activity in atherosclerosis.
研究了ATP对渡边遗传性高脂血症兔主动脉舒张作用未受损害的机制，以阐明动脉粥样硬化过程中内皮水平P2y嘌呤能受体的作用。实验采用12月龄此类兔子的离体胸主动脉进行。强效P2y嘌呤能受体激动剂2-甲硫基ATP未诱导任何内皮依赖性或平滑肌依赖性舒张，因此排除了P2y嘌呤能受体的任何作用。ADP而非AMP通过作用于内皮和平滑肌水平使主动脉舒张。腺苷仅通过作用于平滑肌使血管舒张。因此，ATP和ADP持续的内皮舒张作用并非由于P1或P2y嘌呤能受体的激活，而是可能涉及随着动脉粥样硬化进展而出现的重塑嘌呤能受体位点的激活。该位点可被亚甲蓝拮抗。形态学分析中观察到的内皮单层紊乱可能与动脉粥样硬化中内皮嘌呤能活性的功能重塑有关。
