Document Detail

Effects of exogenous big endothelin-1 on postischemic cardiac dysfunction and norepinephrine overflow in rat hearts.
MedLine Citation:
PMID:  21048781     Owner:  NLM     Status:  In-Data-Review    
Endothelin-1 (ET-1) is involved in norepinephrine (NE) overflow and cardiac dysfunction after myocardial ischemia/reperfusion via the activation of ET(A) receptors. As ET-1 is generated from big ET-1 via endothelin-converting enzyme (ECE), ischemia/reperfusion-induced cardiac injury may be exacerbated by exogenous big ET-1. The aim of this study was to investigate the influence of exogenously applied big ET-1 on ischemia/reperfusion-induced NE overflow and cardiac dysfunction. According to the Langendorff technique, isolated rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. Exogenous big ET-1 (0.1, 0.3 and 1 nM) was perfused, beginning 15 min before ischemia. Unexpectedly, higher doses (0.3 and 1 nM) of big ET-1 significantly improved indices of left ventricular function after ischemia/reperfusion, such as left ventricular developed pressure (LVDP), the maximum value of the first derivative of left ventricular pressure (dP/dt(max)) and left ventricular end diastolic pressure (LVEDP). In addition, big ET-1 significantly suppressed excessive NE overflow in the coronary effluent from the postischemic heart. These effects of big ET-1 were markedly attenuated by treatment with SM-19712 (selective ECE inhibitor) or A-192621 (selective ET(B) receptor antagonist). On the other hand, those were not potentiated even though combined with ABT-627 (selective ET(A) receptor antagonist). From these findings, we suggest that exogenous big ET-1 has beneficial effects on ischemia/reperfusion-induced cardiac injury. It seems likely that big ET-1 is converted to ET-1, locally in the heart, and this ET-1 preferentially binds to ET(B) receptors to exert its related beneficial actions.
Masashi Tawa; Taiki Fukumoto; Mamoru Ohkita; Naoto Yamashita; Ayman Geddawy; Takeshi Imamura; Kazuhide Ayajiki; Tomio Okamura; Yasuo Matsumura
Publication Detail:
Type:  Journal Article     Date:  2010-11-04
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  34     ISSN:  1348-4214     ISO Abbreviation:  Hypertens. Res.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  218-24     Citation Subset:  IM    
1] Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan [2] Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga, Japan.
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