Coronary function and adenosine receptor-mediated responses in ischemic-reperfused mouse heart

被引:25
|
作者
Flood, AJ [1 ]
Willems, L [1 ]
Headrick, JP [1 ]
机构
[1] Griffith Univ, Sch Hlth Sci, Heart Fdn Res Ctr, Southport, Qld 4217, Australia
关键词
adenosine; coronary circulation; ischemia; K-ATP channel; reperfusion; vasoconstriction/dilation; ventricular function;
D O I
10.1016/S0008-6363(02)00329-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: To assess the impact of ischemia-reperfusion (I/R) on coronary function, and the role of endogenous adenosine in modifying post-ischemic vascular function in asanguinous hearts. Methods: Vascular function was studied in Langendorff perfused mouse hearts subjected to 20-25-min ischemia and 30-min reperfusion. Results: Ischemia altered the dependence of flow on work-rate observed in normoxic hearts, and inhibited reflow by mechanisms additional to diastolic compression. Coronary responses were selectively reduced: 2-chloroadenosine and ADP dilated with pEC(50)s of 8.4+/-0.1 and 7.4+/-0.1 in non-ischemic hearts versus 7.7+/-0.1 and 7.1+/-0.1 after 20-min ischemia (P<0.05). Sensitivity was further reduced after 25-min ischemia. Responses to nitroprusside were unaltered. NO-synthase antagonism (50 muM nitro-L-arginine methylester) reduced sensitivities to 2-chloroadenosine and ADP up to 10-fold, and eliminated inhibitory effects of I/R. K-ATP blockade with 5 muM glibenclamide impaired sensitivity pre- and post-ischemia, not eliminating the inhibitory effects of I/R. A, adenosine receptor antagonism with 100 nM 8-cyclopentyl-1,3-dipropylxanthine worsened effects of ischernia on sensitivity. A(2A) adenosine receptor antagonism with 100 nM 8- (-3-chlorostyryl)caffeine reduced post-ischemic flow by 50%, yet paradoxically enhanced post-ischemic contractile recovery. Conclusions: Ischemia modifies vascular control and impairs NO- versus K-ATP-dependent coronary dilation in an asanguinous model. Endogenous adenosine protects against vascular dysfunction via A, receptors, and determines coronary reflow via A(2A) receptors. However, intrinsic A,,,A activation apparently worsens contractile dysfunction. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:161 / 170
页数:10
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