ENDOTHELIN ENHANCES THE CONTRACTILE RESPONSIVENESS OF ADULT-RAT VENTRICULAR MYOCYTES TO CALCIUM BY A PERTUSSIS TOXIN-SENSITIVE PATHWAY

被引:167
作者
KELLY, RA [1 ]
EID, H [1 ]
KRAMER, BK [1 ]
ONEILL, M [1 ]
LIANG, BT [1 ]
REERS, M [1 ]
SMITH, TW [1 ]
机构
[1] HARVARD UNIV,SCH MED,BOSTON,MA 02115
关键词
endothelium; fura-2; inotropy; myocardium; β-adrenergic;
D O I
10.1172/JCI114822
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 rat ventricular cells, endothelin's action was slow in onset but very long lasting with an EC50 of 50 pM that approximates the reported K(D) 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 β-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.
引用
收藏
页码:1164 / 1171
页数:8
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