Adenosine receptor subtypes mediating coronary vasodilation in rat hearts.
Adenosine receptor-mediated coronary vasodilation was studied in isolated hearts from young (1-2 months) and mature (12-18 months) Wistar rats. The nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) induced biphasic concentration-dependant dilation with similar potencies in both age groups (p < 0.05). Despite similar potencies, responses to NECA were significantly depressed by 50% with age. NECA-mediated dilation was unaltered by selective A adenosine receptor (A1AR) antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 nM ) or A adenosine receptor (A2AAR) antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5- ]pyrimidine (SCH 58261, 100 nM ). However, the A2B adenosine receptor (A2B AR) selective antagonist alloxazine (10 microM ) significantly reduced response magnitude to NECA in both age groups. Concentration-response curves to N -2-(4-aminophenyl) ethyladenosine (APNEA) induced biphasic concentration-dependent dilation in hearts from young animals. In the presence of the three combined antagonists, 1 microM DPCPX, 100 nM SCH 58261, and 1 microM alloxazine, the response magnitude was significantly attenuated (p < 0.05). The addition of the A3 adenosine receptor (A3AR) antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191, 100 nM ) to the combined antagonists further attenuated vasodilator responses to APNEA. The results suggest that multiple adenosine receptor subtypes mediate dilation in the rat coronary circulation. NECA mediates vasodilation via the A2BAR subtype, while dilator responses to APNEA in the presence and absence of A1, A2, and A3 ARs antagonists provide evidence for a vasodilator role for A3 ARs in rat coronary circulation. The magnitude of the coronary dilator response is reduced with age and does not involve A2A or A1 ARs.
Hinschen
Andrea K
AK
Heart Foundation Research Center, School of Health Science, Griffith University Gold Coast Campus, Southport, QLD 4215, Australia.
Rose'Meyer
Roselyn B
RB
Headrick
John P
JP
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000145:classification / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
C086112:N(6)-2-(4-aminophenyl)ethyladenosine; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine