NEGATIVE INOTROPIC EFFECTS OF CYTOKINES ON THE HEART MEDIATED BY NITRIC-OXIDE
NEGATIVE INOTROPIC EFFECTS OF CYTOKINES ON THE HEART MEDIATED BY NITRIC-OXIDE
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DOI：
10.1126/science.1631560
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发表时间：
1992-07-17
期刊：
影响因子：
56.9
通讯作者：
SIMMONS, RL
中科院分区：
文献类型：
--
作者：
FINKEL, MS;ODDIS, CV;SIMMONS, RL
研究了促炎细胞因子对哺乳动物心脏收缩力的直接影响。肿瘤坏死因子- α、白细胞介素-6和白细胞介素-2以浓度依赖、可逆的方式抑制离体仓鼠乳头肌的收缩力。一氧化氮合酶抑制剂N(G)-单甲基- l-精氨酸（L-NMMA）阻断了这些负性肌力作用。l -精氨酸逆转了L-NMMA的抑制作用。去除心内膜内皮并没有改变这些反应。这些发现表明，细胞因子的直接负性肌力作用是通过心肌一氧化氮合酶介导的。促炎细胞因子和心肌一氧化氮合酶的调节可能为心脏疾病的治疗提供新的治疗策略。
The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor-alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effectS. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.