期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 41, 期 1, 页码 73-80出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00005344-200301000-00010
关键词
adenosine; age; coronary vessels; rat heart; receptors
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(1) adenosine receptor (A(1)AR) antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 nM) or A(2A) adenosine receptor (A(2A)AR) antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261, 100 nM). However, the A(2B) adenosine receptor (A(2B) AR) selective antagonist alloxazine (10 mu M) significantly reduced response magnitude to NECA in both age groups. Concentration-response curves to N-6-2-(4-aminophenyl) ethyladenosine (APNEA) induced biphasic concentration-dependent dilation in hearts from young animals. In the presence of the three combined antagonists, 1 mu M DPCPX, 100 nM SCH 58261, and 1 mu M alloxazine, the response magnitude was significantly attenuated (p < 0.05). The addition of the A(3) adenosine receptor (A(3)AR) 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 A(2B)AR subtype, while dilator responses to APNEA in the presence and absence of A(1), A(2), and A(3) AR antagonists provide evidence for a vasodilator role for A(3) ARs in rat coronary circulation. The magnitude of the coronary dilator response is reduced with age and does not involve A(2A) or A(1) ARs.
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