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首页> 外文期刊>Pharmacological research: The official journal of The Italian Pharmacological Society >EDHF: new therapeutic targets?
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EDHF: new therapeutic targets?

机译：EDHF：新的治疗靶标？

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摘要

Besides cyclooxygenase and NO-synthase, another distinct endothelial pathway, endothelium-dependent hyperpolarization (EDHF), is involved in the relaxation of the vascular smooth muscle cells. EDHF has been demonstrated unequivocally in various blood vessels from different species, including human, and is likely to play an important role in cardiovascular physiology. This alternative pathway involves the activation of two populations of endothelial potassium channels, the small conductance and intermediate conductance calcium-activated potassium channels (SK(Ca) and IK(Ca), respectively). EDHF-mediated responses are clearly altered in various pathological conditions (ageing, hypertension, atherosclerosis, hypercholesterolemia, heart failure, ischemia-reperfusion, angioplasty, eclampsia, diabetes, sepsis). Therapeutic or adjutant interventions (angiotensin converting enzyme inhibitors, antagonist of the angiotensin receptor, estrogen, omega-3 polyunsaturated fatty acids, polyphenol derivatives, potassium and/or calcium intake) can restore these responses, suggesting that the improvement of the EDHF pathway contributes to the observed beneficial effect of these various substances. However, the improvement or restoration of EDHF responses has not been, yet, the direct purpose of any pharmaceutical effort. Activating endothelial IK(Ca) and/or SK(Ca) or increasing their expression as well as improving myo-endothelial communication, for instance by increasing the expression of connexin(s), could become interesting therapeutic targets.
机译：除环氧合酶和一氧化氮合酶外，另一种独特的内皮途径，即内皮依赖性超极化（EDHF），也参与血管平滑肌细胞的松弛。 EDHF已在包括人类在内的不同物种的各种血管中得到明确证明，并可能在心血管生理学中发挥重要作用。此替代途径涉及激活两个内皮钾通道种群，即小电导和中电导的钙激活钾通道（分别为SK（Ca）和IK（Ca））。 EDHF介导的反应在各种病理状况（年龄，高血压，动脉粥样硬化，高胆固醇血症，心力衰竭，缺血再灌注，血管成形术，子痫，糖尿病，败血症）中均发生明显改变。治疗或辅助干预（血管紧张素转换酶抑制剂，血管紧张素受体拮抗剂，雌激素，ω-3多不饱和脂肪酸，多酚衍生物，钾和/或钙的摄入）可以恢复这些反应，表明EDHF途径的改善有助于观察到的各种物质的有益作用。然而，改善或恢复EDHF应答还不是任何药物努力的直接目的。例如通过增加连接蛋白的表达，激活内皮IK（Ca）和/或SK（Ca）或增加它们的表达以及改善肌-内皮沟通可能成为有趣的治疗靶标。

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