The cellular mechanisms by which adenosine evokes release of nitric oxide from rat aortic endothelium

摘要: Adenosine and nitric oxide (NO) are important local mediators of vasodilatation. The aim this study was to elucidate the mechanisms underlying adenosine receptor-mediated NO release from endothelium. In studies on freshly excised rat aorta, second-messenger systems were pharmacologically modulated by appropriate antagonists while a NO-sensitive electrode used measure adenosine-evoked We showed that A1-mediated requires extracellular Ca2+, phospholipase A2 (PLA2) ATP-sensitive K+ (KATP) channel activation whereas A2A-mediated Ca2+ Ca2+-activated (KCa) channels. Since our previous A1- A2A-receptor-mediated adenylate cyclase (AC), we propose following novel pathways. efflux resulting A1-receptor-coupled KATP-channel facilitates influx which may cause some stimulation endothelial synthase (eNOS). However, increase in [Ca2+]i also stimulates PLA2 liberate arachidonic acid stimulate cyclooxygenase generate prostacyclin (PGI2). PGI2 acts its receptors cAMP, so activating protein kinase A (PKA) phosphorylate activate eNOS release. By contrast, A2A-coupled KCa channels influx, thereby This process be facilitated phosphorylation PKA via action AC increasing cAMP. These pathways mediating vasodilatation during exercise systemic hypoxia when acting an endothelium- NO-dependent manner has been shown important.