Adenosine Receptor Subtypes Mediating Coronary Vasodilation in Rat Hearts

• Published in: Journal of cardiovascular pharmacology Vol. 41; no. 1; pp. 73 - 80
• Main Authors: Hinschen, Andrea K, Rose'Meyer, Roselyn B, Headrick, John P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott Williams & Wilkins, Inc 01-01-2003; Hagerstown, MD Lippincott
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine-5'-(N-ethylcarboxamide) - pharmacology; Adenosinic and purinergic receptors; Aging - physiology; Animals; Biological and medical sciences; Blood vessels and receptors; Cell receptors; Cell structures and functions; Coronary Vessels - drug effects; Fundamental and applied biological sciences. Psychology; Male; Molecular and cellular biology; Rats; Rats, Wistar; Receptors, Purinergic P1 - classification; Receptors, Purinergic P1 - drug effects; Vasodilation - drug effects; Vertebrates: cardiovascular system; Heart; Molecular form; Rat; Rodentia; Smooth muscle; In vitro; Biological activity; Vasodilation; Muscular relaxation; Vertebrata; Mammalia; Adenosine-Age-Coronary vessels-Rat heart-Receptors; Animal; Blood vessel; Myocardium; Circulatory system; Adenosine receptor; Mechanism of action
• DOI: 10.1097/00005344-200301000-00010
• EISSN: 1533-4023
• ISSN: 0160-2446

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 A1 adenosine receptor (A1AR) antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 n M) or A2A adenosine receptor (A2AAR) antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261, 100 n M). However, the A2B adenosine receptor (A2B AR) selective antagonist alloxazine (10 μM) 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 μM DPCPX, 100 n M SCH 58261, and 1 μM 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 n M) 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 AR 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.