Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation
Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation
复制标题
DOI：
10.1152/ajpheart.01035.2005
复制
发表时间：
2006-12-01
影响因子：
4.8
通讯作者：
Tune, Johnathan D.
中科院分区：
文献类型：
--
作者：
Dick, Gregory M.;Katz, Paige S.;Tune, Johnathan D.
脂源性信号分子的血浆水平升高与肥胖、血管内皮功能障碍和冠心病相关;然而，对其直接的冠状血管效应知之甚少。因此，我们研究了一种脂肪细胞因子-β-肾上腺素影响冠状动脉血管张力和内皮功能的机制。在麻醉犬和离体冠状动脉环中进行研究。抵抗素不改变冠状动脉血流量、平均动脉压或心率。抵抗素对乙酰胆碱诱导的动脉环舒张没有影响;然而，抵抗素确实损害缓激肽诱导的舒张。在体内也观察到了选择性损害，因为舒血管肽减弱了缓激肽的血管舒张作用，但没有减弱乙酰胆碱的血管舒张作用。抵抗素对二氢乙锭荧光没有影响，二氢乙锭荧光是超氧化物（O-2（-））产生的指示剂，在超氧化物歧化酶模拟物Tempol存在下，抵抗素对缓激肽诱导的舒张的抑制作用持续存在。为了确定是否有一氧化氮（NO）或三尖杉酯碱（e。例如，在一个实施例中，前列环素; PGI（2）），我们用N-ω-硝基-L-精氨酸甲酯（L-NAME）和吲哚美辛进行实验。在L-NAME或吲哚美辛存在下，Bcln减弱缓激肽诱导的血管舒张的作用持续存在，表明Bcln可能作用于NO或PGI（2）产生上游的细胞信号点。抵抗素诱导的内皮功能障碍不是普遍性的，它与O-2（-）介导的效应或干扰NO或PGI（2）信号传导不一致。抵抗素诱导的损伤的部位尚不清楚，但可能是在缓激肽受体或一氧化氮合酶或环氧合酶附近的密切相关的信号转导机制。
Elevated plasma levels of fat-derived signaling molecules are associated with obesity, vascular endothelial dysfunction, and coronary heart disease; however, little is known about their direct coronary vascular effects. Accordingly, we examined mechanisms by which one adipokine, resistin, affects coronary vascular tone and endothelial function. Studies were conducted in anesthetized dogs and isolated coronary artery rings. Resistin did not change coronary blood flow, mean arterial pressure, or heart rate. Resistin had no effect on acetylcholine-induced relaxation of artery rings; however, resistin did impair bradykinin-induced relaxation. Selective impairment was also observed in vivo, as resistin attenuated vasodilation to bradykinin but not to acetylcholine. Resistin had no effect on dihydroethidium fluorescence, an indicator of superoxide (O-2(-)) production, and the inhibitory effect of resistin on bradykinin-induced relaxation persisted in the presence of Tempol, a superoxide dismutase mimetic. To determine whether resistin impaired production of and/or responses to nitric oxide (NO) or prostaglandins ( e. g., prostacyclin; PGI(2)), we performed experiments with N-omega-nitro-L-arginine methyl ester (L-NAME) and indomethacin. The effect of resistin to attenuate bradykinin-induced vasodilation persisted in the presence of L-NAME or indomethacin, suggesting resistin may act at a cell signaling point upstream of NO or PGI(2) production. Resistin-induced endothelial dysfunction is not generalized, and it is not consistent with effects mediated by O-2(-) or interference with NO or PGI(2) signaling. The site of the resistin-induced impairment is unknown but may be at the bradykinin receptor or a closely associated signal transduction machinery proximal to NO synthase or cyclooxygenase.