RESPONSES OF CEREBRAL ARTERIOLES IN DIABETIC RATS TO ACTIVATION OF ATP-SENSITIVE POTASSIUM CHANNELS
RESPONSES OF CEREBRAL ARTERIOLES IN DIABETIC RATS TO ACTIVATION OF ATP-SENSITIVE POTASSIUM CHANNELS
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DOI：
10.1152/ajpheart.1993.265.1.h152
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发表时间：
1993-07-01
影响因子：
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通讯作者：
FARACI, FM
中科院分区：
文献类型：
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作者：
MAYHAN, WG;FARACI, FM
本研究的目的是确定在糖尿病期间软膜小动脉对ATP敏感性钾通道激活的反应是否改变。我们测量了非糖尿病和糖尿病大鼠（链脲佐菌素; 50-60 mg/kg ip;链脲佐菌素后3-4个月研究）体内软脑膜小动脉直径对RP 52891（ATP敏感性钾通道激活剂）的反应变化。RP 52891（1.0 μ M）使非糖尿病大鼠的软脑膜小动脉扩张16 +/- 1%，但使糖尿病大鼠的软脑膜小动脉收缩2 +/- 2%（平均值+/- SE; P < 0.05，与非糖尿病大鼠的反应相比）。非糖尿病大鼠对RP 52891的软脑膜小动脉扩张反应可被格列本脲（1.0 μ M）抑制，但不被N（G）-单甲基-L-精氨酸（1.0 μ M）、蜂毒肽（0.1 μ M）或Charybdotoxin（50 nM）改变。因此，软脑膜小动脉对RP 52891的反应性扩张似乎是由于ATP敏感性钾通道的激活，而不涉及一氧化氮或钙激活钾通道。为了确定糖尿病大鼠对RP 52891的软脑膜小动脉扩张受损是否与糖尿病对血管扩张的非特异性作用有关，我们测量了非糖尿病和糖尿病大鼠对硝酸甘油的软脑膜小动脉直径。硝酸甘油（1.0 μ M）使非糖尿病大鼠软脑膜小动脉扩张12 +/-1%，糖尿病大鼠扩张16 +/-2%（P > 0.05）。因此，RP 52891引起的糖尿病大鼠软脑膜小动脉扩张受损也与糖尿病对血管扩张的非特异性作用无关。本研究的结果表明，ATP敏感性钾通道在体内脑小动脉中是功能性的，并且在糖尿病期间受损。
The goal of this study was to determine whether responses of pial arterioles to activation of ATP-sensitive potassium channels are altered during diabetes mellitus. We measured changes in diameter of pial arterioles in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg ip; studied 3-4 mo after streptozotocin) in response to RP52891, an activator of ATP-sensitive potassium channels. RP52891 (1.0 muM) dilated pial arterioles in nondiabetic rats by 16 +/- 1% but constricted pial arterioles in diabetic rats by 2 +/- 2% (means +/- SE; P < 0.05 vs. response in nondiabetic rats). Dilatation of pial arterioles in nondiabetic rats in response to RP52891 was inhibited by glibenclamide (1.0 muM) but was not altered by N(G)-monomethyl-L-arginine (1.0 muM), apamin (0.1 muM), or charybdotoxin (50 nM). Thus dilatation of pial arterioles in response to RP52891 appears to be due to activation of ATP-sensitive potassium channels and does not involve nitric oxide or calcium-activated potassium channels. To determine whether impaired dilatation of pial arterioles in response to RP52891 in diabetic rats was related to a nonspecific effect of diabetes mellitus on vasodilatation, we measured diameter of pial arterioles in nondiabetic and diabetic rats in response to nitroglycerin. Nitroglycerin (1.0 muM) dilated pial arterioles by 12 +/- 1 % in nondiabetic rats and 16 +/- 2 % in diabetic rats (P > 0.05). Thus impaired dilatation of pial arterioles in diabetic rats in response to RP52891 also is not related to a nonspecific effect of diabetes mellitus on vasodilatation. The findings of the present study suggest that ATP-sensitive potassium channels are functional in cerebral arterioles in vivo and are impaired during diabetes mellitus.