HYPOTENSIVE RESPONSES TO THE PUTATIVE ADENOSINE A(3) RECEPTOR AGONIST N-6-2-(4-AMINOPHENYL)-ETHYLADENOSINE IN THE RAT

The hypotensive response to the putative adenosine A(3) receptor agonist, N-6-2-(4-aminophenyl)ethyladenosine (APNEA), has been further investigated. In pithed rats with blood pressures maintained at normal values with angiotensin II, the hypotensive response to APNEA was resistant to blockade by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) at a dose of 0.5 mg kg (1.7 mu mol kg) iv, which abolished the bradycardia to APNEA and that to the prototype A(1) receptor agonist, N-6-cyclopentyladenosine (CPA). The xanthine-resistant hypotensive responses to APNEA were broadly similar in pithed animals whose blood pressures were maintained by phenylephrine, clonidine, or the inhibitor of nitric oxide (NO) synthase, N-G-nitro-L-arginine methyl ester (L-NAME). The blocker of ATP-dependent potassium (K-ATP) channels, glibenclamide, did not affect the hypotensive response to APNEA in animals infused with angiotensin II. Thus, the xanthine-resistant hypotensive response to APNEA is not an effect dependent on a particular agonist-receptor interaction. Neither the release of NO, newly synthesized from L-arginine, nor activation of glibenclamide-sensitive K-ATP channels can explain the putative A(3) receptor-mediated hypotensive response to APNEA. (C) 1993 Wiley-Liss, Inc.