ENDOTHELIN ENHANCES THE CONTRACTILE RESPONSIVENESS OF ADULT-RAT VENTRICULAR MYOCYTES TO CALCIUM BY A PERTUSSIS TOXIN-SENSITIVE PATHWAY
ENDOTHELIN ENHANCES THE CONTRACTILE RESPONSIVENESS OF ADULT-RAT VENTRICULAR MYOCYTES TO CALCIUM BY A PERTUSSIS TOXIN-SENSITIVE PATHWAY
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DOI：
10.1172/jci114822
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发表时间：
1990-10-01
影响因子：
15.9
通讯作者：
SMITH, TW
中科院分区：
文献类型：
--
作者：
KELLY, RA;EID, H;SMITH, TW
长期以来，人们一直认为调节心肌收缩力的主要影响因素是肌纤维的机械负荷程度和自主神经系统的活动。然而，最初发现于血管内皮的血管活性肽内皮素是哺乳动物心肌中最有效的正性肌力药物之一。在分离的成年大鼠心室细胞中，内皮素的作用开始缓慢，但持续时间很长，EC 50为50 pM，接近大鼠心脏中肽对其受体的KD。当缓冲液灌流分离的单个Fura-2负载的心肌细胞的钙活性在1.5 Hz起搏从0.1到0.9 mM [Ca 2 +] 0变化时，100 pM内皮素增加收缩幅度，而舒张或收缩[Ca 2 +]i没有显著变化，因此似乎使肌丝对细胞内钙敏感。百日咳毒素，或先前暴露于β-肾上腺素能激动剂，减少或消除内皮素诱导的心肌细胞收缩力的增加。内皮素的这种新的和有效的药理作用指出了局部旁分泌因子在控制心脏收缩功能中的潜在重要性，这些因子可能来自微血管内皮或内皮细胞。
It has long been assumed that the primary influences regulating cardiac contractility are the extent of mechanical loading of muscle fibers and the activity of the autonomic nervous system. However, the vasoactive peptide endothelin, initially found in vascular endothelium, is among the most potent positively inotropic agents yet described in mammalian myocardium. In isolated adult rat ventricular cells, endothelin''s action was slow in onset but very long lasting with an EC50 of 50 pM that approximates the reported KD of the peptide for its receptor in rat heart. When the calcium activity of the buffer superfusing isolated single fura-2-loaded myocytes paced at 1.5 Hz was varied from 0.1 to 0.9 mM [Ca2+]o, 100 pM endothelin increased contractile amplitude with no significant change in diastolic or systolic [Ca2+]i, thus appearing to sensitize the myofilaments to intracellular calcium. Pertussis toxin, or prior exposure to a .beta.-adrenergic agonist, reduced or abolished the increase in myocyte contractility induced by endothelin. This novel and potent pharmacologic action of endothelin points to the potential importance of local, paracrine factors, perhaps derived from microvascular endothelium or endocardium, in the control of the contractile function of the heart.