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Inhibition of myocardial endothelin pathway improves long-term survival in heart failure.

机译:抑制心肌内皮途径改善心力衰竭的长期生存。

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摘要

Occlusion of the diseased coronary artery in humans causes acute myocardial infarction, survivors of which have a high risk for the development of chronic heart failure. Cardiac myocytes and vascular endothelial cells produce endothelin-1 (refs 2-4), which increases the contractility of cardiac muscle and of vascular smooth muscle cells. Endothelin-1 also exerts long-term effects such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. Production of endothelin-1 is markedly increased in the myocardium of rats with heart failure, and acute application of an endothelin-receptor antagonist decreases myocardial contractility in such rats, indicating that myocardial endothelin-1 may help to support contractility of the failing heart. But we report here that the upregulated myocardial endothelin system may contribute to the progression of chronic heart failure, because long-term treatment with an endothelin-receptor antagonist greatly improved the survival of rats with chronic heart failure. This beneficial effect was accompanied by significant amelioration of left ventricular dysfunction and prevention of ventricular remodelling, in which there is usually an increase in the ventricular mass and cavity enlargement of the ventricle.
机译:阻塞人类患病的冠状动脉会导致急性心肌梗塞,其幸存者极有可能患上慢性心力衰竭。心肌细胞和血管内皮细胞产生内皮素-1(参考文献2-4),增加了心肌和血管平滑肌细胞的收缩力。内皮素-1还发挥诸如心肌肥大之类的长期作用,并引起心肌细胞的细胞损伤。心力衰竭大鼠心肌中内皮素-1的产量显着增加,并且急性应用内皮素受体拮抗剂会降低此类大鼠的心肌收缩力,这表明心肌内皮素-1可能有助于支持衰竭心脏的收缩力。但是我们在这里报告说,心肌内皮素系统的上调可能有助于慢性心力衰竭的进展,因为长期使用内皮素-受体拮抗剂治疗可以大大改善慢性心力衰竭大鼠的存活率。这种有益效果伴随着左心室功能障碍的明显改善和防止心室重构,其中通常会增加心室质量并增加心室腔。

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