Role of oxidative metabolism on endothelium-dependent vascular relaxation of isolated vessels

被引:18
作者
CappelliBigazzi, M [1 ]
Battaglia, C [1 ]
Pannain, S [1 ]
Chiariello, M [1 ]
Ambrosio, G [1 ]
机构
[1] UNIV PERUGIA, SCH MED, DIV CARDIOL, I-06100 PERUGIA, ITALY
关键词
endothelium; vasodilation; oxidative metabolism; glycolysis;
D O I
10.1006/jmcc.1996.0286
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The obligatory role of endothelium in mediating vasodilator response to numerous humoral agents has been definitely accepted. However, the chemical identity of endothelium-derived relaxing factor(s) (EDRF) and the mechanisms underlying its synthesis and release remain unclear. Much evidence suggests a compartmentalization of ATP into cells, such that ATP derived from glycolysis or from oxidative metabolism is used for different cellular functions. To investigate which energy source (i.e. oxidative v glycolytic metabolism) is preferentially used for the biosynthesis and/or release of EDRF, rings of rabbit thoracic aorta were studied in organ chambers. After preconstriction with PGF(2 alpha), inhibition of glycolysis with either iodoacetate (300 mu M) (n = 6) or 2-deoxyglucose (20 mM) (n = 6) did not affect concentration-response curve to the endothelium-dependent agent acetylcholine. In contrast, inhibition of oxidative metabolism with either 1 mM amytal or 5 mu M rotenone markedly impaired relaxation to acetylcholine. In fact, maximal relaxation was 75 +/- 5% in control rings (n = 6), and 42 +/- 7% (P < 0.01) in amytal-treated rings (n = 6), whereas rotenone converted acetylcholine relaxation into constriction (n = 6; P < 0.001). The effect of amytal on endothelium-dependent relaxation was reversible, suggesting that endothelial cells were not damaged by the inhibitor. Amytal also markedly reduced endothelium-mediated relaxation to ADP (37 +/- 6%; P < 0.05; n = 5), as well as to the calcium ionophore A23187. Neither mitochondrial inhibitor affected relaxation to nitroglycerin, an endothelium-independent agent. Finally, amytal did not affect relaxation to S-nitrosocysteine (a recently proposed EDRF) (n = 5), suggesting that the effects on acetylcholine and ADP responses were not due to non-specific interferences with EDRF once released from endothelial cells. In conclusion, our data demonstrate that the active process of biosynthesis and/or release of EDRF requires energy derived mainly from mitochondrial oxidative metabolism. (C) 1997 Academic Press Limited.
引用
收藏
页码:871 / 879
页数:9
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