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

The hypotensive response to the putative adenosine A(3) receptor agoni st, N-6-2-(4-aminophenyl)ethyladenosine (APNEA), has been further inve stigated. In pithed rats with blood pressures maintained at normal val ues with angiotensin II, the hypotensive response to APNEA was resista nt 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 A PNEA and that to the prototype A(1) receptor agonist, N-6-cyclopentyla denosine (CPA). The xanthine-resistant hypotensive responses to APNEA were broadly similar in pithed animals whose blood pressures were main tained 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 af fect the hypotensive response to APNEA in animals infused with angiote nsin 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 act ivation of glibenclamide-sensitive K-ATP channels can explain the puta tive A(3) receptor-mediated hypotensive response to APNEA. (C) 1993 Wi ley-Liss, Inc.