Selective attenuation of isoproterenol-stimulated arrhythmic activity by a partial agonist of adenosine A1 receptor.
Selective attenuation of isoproterenol-stimulated arrhythmic activity by a partial agonist of adenosine A1 receptor.
复制标题
通过腺苷 A1 受体的部分激动剂选择性减弱异丙肾上腺素刺激的心律失常活性。
DOI：
10.1161/hc0102.101392
复制
发表时间：
2002
期刊：
影响因子：
37.8
通讯作者：
Belardinelli,Luiz
中科院分区：
文献类型：
--
作者：
Song,Yejia;Wu,Lin;Shryock,JohnC;Belardinelli,Luiz
背景：本研究的目的是检验腺苷a1受体（A1AdoR）的部分激动剂可能导致儿茶酚胺诱导的室性心律失常活动的衰减大于收缩性的假设。方法与结果：测定CVT-2759和A1AdoR的部分和完全激动剂腺苷对异丙肾上腺素刺激的豚鼠离体心室肌细胞的心律失常活性和收缩力的影响。CVT-2759 （10 μmol/L）和腺苷（10 μmol/L）显著抑制异丙肾上腺素诱导的心律失常活动（后收缩和瞬态内向电流），但不降低抽搐缩短幅度和L型Ca2+电流。当完全激动剂腺苷浓度从10 μmol/L增加到100 μmol/L时，抽搐缩短和后收缩明显减弱，而部分激动剂CVT-2759浓度从10 μmol/L增加到100 μmol/L则无明显减弱。CVT-2759还能显著抑制异丙肾上腺素诱导的离体心脏自发心室跳动。与腺苷相比，CVT-2759既没有激活腺苷敏感的K+电流，也没有缩短心房APD的持续时间。结论：目前的结果支持这一假设，并提示A1AdoR部分激动剂在心律失常治疗中的潜在作用。
Background—The goal of this study was to examine the hypothesis that a partial agonist of the adenosine A1receptor (A1AdoR) may cause a greater attenuation of catecholamine-induced ventricular arrhythmic activity than of contractility.Methods and Results—The effects of CVT-2759 and adenosine, a partial and a full agonist of the A1AdoR, on isoproterenol-stimulated arrhythmic activity and contractility of guinea pig isolated ventricular myocytes were determined. CVT-2759 (10 μmol/L) and adenosine (10 μmol/L) significantly inhibited isoproterenol-induced arrhythmic activity (aftercontraction and transient inward current) but did not reduce the amplitudes of twitch shortening and L-type Ca2+current. Increasing the concentration of the full agonist adenosine from 10 to 100 μmol/L, however, caused significant attenuation of twitch shortening as well as aftercontractions, whereas increasing the concentration of the partial agonist CVT-2759 from 10 to 100 μmol/L did not. CVT-2759 also significantly inhibited isoproterenol-induced spontaneous ventricular beats in isolated hearts. In contrast to adenosine, CVT-2759 neither activated adenosine-sensitive K+current nor shortened the duration of the atrial APD.Conclusions—The present results support the hypothesis and suggest a potential role for a partial agonist of the A1AdoR in the treatment of cardiac arrhythmias.