Hypotensive and renal vasodilator effects of carbocyclic adenosine (aristeromycin) in anesthetized spontaneously hypertensive rats

EW Dunham and R Vince

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.

Volume 238, Issue 3, pp. 954-959, 09/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics