Sakai S, Miyauchi T, Kobayashi M, Yamaguchi I, Goto K, Sugishita Y
Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Nature. 1996 Nov 28;384(6607):353-5. doi: 10.1038/384353a0.
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.
人类病变冠状动脉闭塞会导致急性心肌梗死，其幸存者患慢性心力衰竭的风险很高。心肌细胞和血管内皮细胞会产生内皮素-1（参考文献2-4），它会增加心肌和血管平滑肌细胞的收缩性。内皮素-1还会产生诸如心肌肥大等长期影响，并导致心肌细胞发生细胞损伤。在心力衰竭大鼠的心肌中，内皮素-1的产生显著增加，急性应用内皮素受体拮抗剂可降低此类大鼠的心肌收缩性，这表明心肌内皮素-1可能有助于维持衰竭心脏的收缩性。但我们在此报告，上调的心肌内皮素系统可能会促使慢性心力衰竭的进展，因为长期使用内皮素受体拮抗剂可显著提高慢性心力衰竭大鼠的存活率。这种有益作用伴随着左心室功能障碍的显著改善以及心室重构的预防，心室重构通常表现为心室质量增加和心室腔扩大。
