Dunham E W, Vince R
J Pharmacol Exp Ther. 1986 Sep;238(3):954-9.
Systemic arterial pressure and renal blood flow were measured in pentobarbital-anesthetized spontaneously hypertensive rats to assess the influence and mechanism of action of metabolically stable adenosine analogs on renal hemodynamics. (-)-Aristeromycin (carbocyclic adenosine; CA), a model carbocyclic nucleoside, was characterized with respect to adenosine receptor pharmacology by comparison to the effects elicited by the prototypic adenosine analogs 5'-N-ethylcarboxamide adenosine (NECA; an adenosine A1 and A2 receptor agonist) and N6-cyclohexyl adenosine (an adenosine A1 agonist). Intravenous bolus injections of CA and NECA caused dose-dependent hypotension and renal vasodilatation. Although CA and NECA were equally efficacious hypotensive agents, NECA was approximately 100-fold more potent than CA. CA was a more efficacious renal vasodilator than NECA. In contrast, at doses which had minimal effects on systemic arterial pressure, N6-cyclohexyl adenosine decreased renal blood flow. The hypotensive and renovascular effects of the adenosine analogs but not those of a control vasodilator, methacholine, were attenuated by i.v. administration of the xanthines aminophylline and 8-phenyltheophylline; thus, the effects of the nucleosides on renal blood flow in vivo appear to be attributable in part to activation of adenosine receptors. The profile of cardiovascular effects caused by CA suggests that this agent acts primarily as an adenosine A2 receptor agonist.
在戊巴比妥麻醉的自发性高血压大鼠中测量了体循环动脉压和肾血流量，以评估代谢稳定的腺苷类似物对肾血流动力学的影响及其作用机制。通过与原型腺苷类似物5'-N-乙基羧酰胺腺苷（NECA；一种腺苷A1和A2受体激动剂）和N6-环己基腺苷（一种腺苷A1激动剂）所引发的效应进行比较，对模型碳环核苷（-）-阿糖腺苷（碳环腺苷；CA）的腺苷受体药理学特性进行了表征。静脉推注CA和NECA会引起剂量依赖性低血压和肾血管舒张。尽管CA和NECA作为降压剂的效力相当，但NECA的效力约为CA的100倍。CA作为肾血管舒张剂比NECA更有效。相比之下，在对体循环动脉压影响最小的剂量下，N6-环己基腺苷会降低肾血流量。静脉注射黄嘌呤氨茶碱和8-苯基茶碱可减弱腺苷类似物的降压和肾血管作用，但对照血管舒张剂乙酰甲胆碱的作用不受影响；因此，核苷对体内肾血流的影响似乎部分归因于腺苷受体的激活。CA所引起的心血管效应表明，该药物主要作为腺苷A2受体激动剂起作用。
