Adenosine receptor subtypes mediating coronary vasodilation in rat hearts

被引:55
作者
Hinschen, AK [1 ]
Rose'Meyer, RB [1 ]
Headrick, JP [1 ]
机构
[1] Griffith Univ, Sch Hlth Sci, Heart Fdn Res Ctr, Southport, Qld 4215, Australia
关键词
adenosine; age; coronary vessels; rat heart; receptors;
D O I
10.1097/00005344-200301000-00010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:73 / 80
页数:8
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