Arrhythmogenic action of endothelin-1(1-31) through conversion to endothelin-1(1-21).
Endothelin (ET)-1(1-21) is known to play an important role in the pathogenesis of acute ischemic arrhythmia. In the present study, we attempted to determine whether administration of ET-1(1-31) would result in arrhythmia in perfused isolated rat hearts. Forty-eight Sprague-Dawley rats weighing approximately 250-350 g were randomized into 6 groups. Heart was isolated and perfused in a Langendorff mode. The effects of ET-1(1-31) on arrhythmia, heart rate, coronary flow, and heart function were analyzed. Perfusion with 1 nM ET-1(1-31) resulted in frequent ventricular ectopic beats (VEBs) and ventricular tachycardia (VT). Overall VEB was 128.0 (approximately 66.0-1015.0), and the arrhythmia score (AS) was 2.18 +/- 0.87; both were significantly higher than those of the control group (P < 0.01). Pretreatment with perfusion of 10 nM of the ETA-receptor antagonist BQ(123) markedly attenuated the occurrence of VEB and VT induced by ET-1(1-31). AS in 10 nM BQ123 group was significantly lower than that in 1 nM ET-1(1-31) group (P < 0.01). The arrhythmia induced by 1 nM ET-1(1-31) was partially but significantly reduced by phosphoramidon (1 microM), a neutral endopeptidase/ET-converting enzyme inhibitor. ET-1(1-31) per se caused arrhythmia in perfused isolated rat hearts. This arrhythmogenic action is in part mediated by ET(A) receptor and may be attributed mainly to the conversion of ET-1(1-31) to ET-1(1-21.).
Ren
An-Jing
AJ
Department of Physiology, Basic Medical College, Second Military Medical University, Shanghai, China.
Yuan
Xin
X
Lin
Li
L
Xu
Jing
J
Chen
Ting
T
Wang
Wei-Zhong
WZ
Yan
Xiao-Hong
XH
Qing
Yong-Wen
YW
Tang
Chao-Shu
CS
Yuan
Wen-Jun
WJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000517:prevention & control; D019332:Endothelin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D010477:Perfusion; D011480:Protease Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D019332:Endothelin-1; D006020:Glycopeptides; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon