Tabrizchi R, Lupichuk S M
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Oct;352(4):412-8. doi: 10.1007/BF00172778.
Adenosine and adenosine triphosphate (ATP) induced vasodilatation was studied in isolated rat perfused mesenteric artery at constant flow. Decrease in perfusion pressure was measured after induction of tone by continuous infusion with phenylephrine (5-7 microM). Adenosine and ATP caused dose-dependent vasodilation. Following infusion with selective A2 adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX) (10 microM), or non-selective adenosine receptor antagonist, theophylline (30 microM), vasodilation produced by adenosine were significantly reduced at lower doses. Responses to adenosine were not affected by pretreatment of tissues with either the P2-purinoceptor desensitizing agent, alpha, beta methylene ATP (30 microM), or the P2-purinoceptor antagonist, suramin (10 microM). In contrast, both alpha, beta methylene ATP and suramin significantly attenuate relaxation produced by ATP. Further, it was found that relaxation elicited by either adenosine or ATP was not significantly affected by the presence of glibenclamide (30 microM). Vasodilatation induced by adenosine and ATP was greatly reduced in denuded arteries but more so for ATP than adenosine. It is concluded that adenosine-mediated vasodilatation may hardly be due to the stimulation of A2 adenosine receptors and is strongly dependent on the presence of functional endothelium whereas ATP-mediated vasodilator responses were mediated via the activation of P2-purinoceptors and appeared to be entirely dependent upon the presence of functional endothelium. Further, vasodilator responses to neither adenosine nor ATP were sensitive to inhibition by the potassium channel blocker glibenclamide, in isolated mesenteric perfused bed. This would imply that ATP-sensitive potassium channels were not involved in adenosine and ATP mediated vasodilatation.
在恒流条件下，对分离的大鼠灌注肠系膜动脉中腺苷和三磷酸腺苷（ATP）诱导的血管舒张进行了研究。通过持续输注去氧肾上腺素（5 - 7微摩尔）诱导血管张力后，测量灌注压力的降低情况。腺苷和ATP引起剂量依赖性血管舒张。在输注选择性A2腺苷受体拮抗剂3,7 - 二甲基 - 1 - 炔丙基黄嘌呤（DMPX）（10微摩尔）或非选择性腺苷受体拮抗剂茶碱（30微摩尔）后，较低剂量的腺苷诱导的血管舒张明显减弱。用P2嘌呤受体脱敏剂α,β - 亚甲基ATP（30微摩尔）或P2嘌呤受体拮抗剂苏拉明（10微摩尔）预处理组织，对腺苷的反应不受影响。相反，α,β - 亚甲基ATP和苏拉明均显著减弱ATP产生的舒张作用。此外，发现无论是腺苷还是ATP引起的舒张作用，在存在格列本脲（30微摩尔）时均未受到显著影响。在去内皮的动脉中，腺苷和ATP诱导的血管舒张大大减弱，但ATP比腺苷更明显。结论是，腺苷介导的血管舒张可能几乎不是由于A2腺苷受体的刺激，并且强烈依赖于功能性内皮的存在，而ATP介导的血管舒张反应是通过P2嘌呤受体的激活介导的，并且似乎完全依赖于功能性内皮的存在。此外，在分离的肠系膜灌注床中，对腺苷和ATP的血管舒张反应均对钾通道阻滞剂格列本脲的抑制不敏感。这意味着ATP敏感性钾通道不参与腺苷和ATP介导的血管舒张。
