Arrhythmogenic Action of Endothelin-1 1–31 Through Conversion to Endothelin-1 1

Abstract

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 ~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 (~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 BQ₁₂₃ 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 μM), 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.

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Arrhythmogenic Action of Endothelin-1 1–31 Through Conversion to Endothelin-1 1–21

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