Endothelium-dependent tolerance to ethanol-induced contraction of rat aorta: effect of inhibition of EDRF action and nitric oxide synthesis.
Endothelium-dependent tolerance to ethanol-induced contraction of rat aorta: effect of inhibition of EDRF action and nitric oxide synthesis.
复制标题
内皮依赖性对乙醇诱导的大鼠主动脉收缩的耐受性：EDRF 作用和一氧化氮合成的抑制作用。
DOI：
10.1111/j.1530-0277.1992.tb00636.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Knych,ET
中科院分区：
文献类型：
--
作者：
Knych,ET
体外乙醇诱导主动脉剂量依赖性收缩。对乙醇这种作用的耐受性通过乙醇中毒2天的动物主动脉中剂量反应曲线的显著偏移表示。主动脉中耐受性的表达取决于功能性内皮细胞的存在，这表明耐受性部分由内皮源性舒张因子（EDRF）介导。为了验证这一假设，研究了三种EDRF作用抑制剂和一氧化氮合成抑制剂改变对乙醇诱导的主动脉收缩耐受性的能力。在体外用棉酚（10 - 6- 10 - 5 M）、邻苯三酚（10 - 5 M）、血红蛋白（10 - 6 M）和NG-硝基-L-精氨酸（NOARG，10 - 4 M）预处理主动脉环可抑制卡巴胆碱诱导的内皮依赖性舒张。超氧化物歧化酶（SOD，45单位/ml）可逆转邻苯三酚对卡巴胆碱诱导舒张的抑制作用。用棉酚、连苯三酚、血红蛋白或NOARG对乙醇处理大鼠的环进行体外预处理，可抑制乙醇耐受性的表达，使乙醇剂量反应曲线移至对照值。SOD可逆转邻苯三酚预处理的效应。所有拮抗剂均未显著改变对照动物主动脉环的乙醇剂量反应曲线。这些数据支持这样的假设：对乙醇诱导的主动脉收缩的耐受性是由内皮细胞释放EDRF介导的。
In vitro ethanol induces a dose‐dependent contraction of the aorta. Tolerance to this effect of ethanol is expressed by a rightward shift of the dose‐response curve in aorta from animals intoxicated with ethanol for 2 days. The expression of tolerance in the aorta is dependent upon the presence of functional endothelial cells which suggests that tolerance is mediated, in part, by endothelium‐derived relaxing factor (EDRF). To test this hypothesis, three inhibitors of EDRF action and an inhibitor of nitric oxide synthesis were studied for their ability to alter tolerance to ethanol‐induced contraction of the aorta. In vitro pretreatment of aortic rings with gossypol (10‐6– 10‐5M), pyrogallol (10‐5M), hemoglobin (10‐6M), and NG‐nitro‐L‐arginine (NOARG, 10‐4M) inhibited endothelium‐dependent relaxation induced by carbachol. The inhibition of carbachol‐induced relaxation produced by pyrogallol was reversed by superoxide dismutase (SOD, 45 units/ml). In vitro pretreatment of rings obtained from ethanol‐treated rats with gossypol, pyrogallol, hemoglobin, or NOARG inhibited the expression of ethanol tolerance, shifting the ethanol dose‐response curve to control values. SOD reversed the effect of pyrogallol pretreatment. None of the antagonists significantly altered the ethanol dose‐response curve of aortic rings obtained from control animals. These data support the hypothesis that tolerance to ethanol‐induced contraction of the aorta is mediated by the release of EDRF from endothelial cells.