Endothelin (ET)-11–21 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-11–31 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-11–31 on arrhythmia, heart rate, coronary flow, and heart function were analyzed. Perfusion with 1 n M ET-11–31 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 n M of the ETA-receptor antagonist BQ123 markedly attenuated the occurrence of VEB and VT induced by ET-11–31. AS in 10 n M BQ123 group was significantly lower than that in 1 n M ET-11–31 group ( P < 0.01). The arrhythmia induced by 1 n M ET-11–31 was partially but significantly reduced by phosphoramidon (1 μ M), a neutral endopeptidase/ET-converting enzyme inhibitor. ET-11–31 per se caused arrhythmia in perfused isolated rat hearts. This arrhythmogenic action is in part mediated by ETA receptor and may be attributed mainly to the conversion of ET-11–31 to ET-11–21.

中文翻译：

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Endothelin-11-31 转化为 Endothelin-11-21 的致心律失常作用

内皮素 (ET)-11–21已知在急性缺血性心律失常的发病机制中发挥重要作用。在本研究中，我们试图确定给予 ET-1 是否1–31会导致灌注离体大鼠心脏出现心律失常。体重约 250-350 克的 48 只 Sprague-Dawley 大鼠被随机分为 6 组。心脏被分离并以 Langendorff 模式灌注。ET-1的作用1–31分析心律失常、心率、冠脉流量和心功能。用 1 n M ET-1 灌注1–31导致频繁的室性异位搏动（VEB）和室性心动过速（VT）。总体 VEB 为 128.0 (~66.0–1015.0)，心律失常评分 (AS) 为 2.18 ± 0.87；均显着高于对照组（P<0.01）。灌注 10 n M ETA 受体拮抗剂 BQ 进行预处理123显着减弱 ET-1 诱导的 VEB 和 VT 的发生1–31。10 n M BQ 中的 AS123组显着低于 1 n M ET-1 组1–31组（P<0.01）。1 n M ET-1引起的心律失常1–31被中性内肽酶/ET 转换酶抑制剂磷酸酰胺 (1 μ M) 部分但显着降低。ET-11–31其本身引起灌注离体大鼠心脏的心律失常。这种致心律失常作用部分是由 ET 介导的A受体，可能主要归因于 ET-1 的转化1–31至 ET-11-21。