Alterations in endothelium-dependent hyperpolarization and relaxation in mesenteric arteries from streptozotocin-induced diabetic rats

被引:131
作者
Fukao, M [1 ]
Hattori, Y [1 ]
Kanno, M [1 ]
Sakuma, I [1 ]
Kitabatake, A [1 ]
机构
[1] HOKKAIDO UNIV,SCH MED,DEPT CARDIOVASC MED,SAPPORO,HOKKAIDO 060,JAPAN
关键词
diabetes mellitus; acetylcholine; membrane potential; hyperpolarization; vascular smooth muscle; vasodilatation;
D O I
10.1038/sj.bjp.0701258
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The aim of this study was to determine whether endothelium-dependent hyperpolarization and relaxation are altered during experimental diabetes mellitus. Membrane potentials were recorded in mesenteric arteries from rats with streptozotocin-induced diabetes and age-matched controls. The resting membrane potentials were not significantly different between control and diabetic mesenteric arteries (-55.3+/-0.5 vs -55.6+/-0.4 mV). However, endothelium-dependent hyperpolarization produced by acetylcholine (ACh; 10(-8)-10(-5) M) was significantly diminished in amplitude in diabetic arteries compared with that in controls (maximum -10.4+/-1.1 vs -17.2+/-0.8 mV). Furthermore, the hyperpolarizing responses of diabetic arteries were more transient. 2 ACh-induced hyperpolarization observed in control and diabetic arteries remained unaltered even after treatment with 3 x 10(-4) M N-G-nitro-L-arginine (L-NOARG), 10(-5) M indomethacin or 60 u ml(-1) superoxide dismutase. 3 Endothelium-dependent hyperpolarization with 10(-6) M A23187, a calcium ionophore, was also decreased in diabetic arteries compared to controls (-8.3+/-1.4 vs -18.0+/-1.9 mV). However, endothelium-independent hyperpolarizing responses to 10(-6) M pinacidil, a potassium channel opener, were similar in control and diabetic arteries (-20.0+/-1.4 vs -19.2+/-1.1 mV). 4 The altered endothelium-dependent hyperpolarizations in diabetic arteries were almost completely prevented by insulin therapy. Endothelium-dependent relaxations by ACh in the presence of 10(-4) M L-NOARG and 10(-5) M indomethacin in diabetic arteries were also reduced and more transient compared to controls. 5 These data indicate that endothelium-dependent hyperpolarization is reduced by diabetes, and this would, in part, account for the impaired endothelium-dependent relaxations in mesenteric arteries from diabetic rats.
引用
收藏
页码:1383 / 1391
页数:9
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