Ramesh C V, Malarvannan P, Jayakumar R, Jayasundar S, Puvanakrishnan R
Department of Biotechnology, Central Leather Research Institute, Adyar, Madras, India.
Mol Cell Biochem. 1998 Oct;187(1-2):173-82. doi: 10.1023/a:1006835526608.
Isoproterenol hydrochloride (ISO), a beta adrenergic agonist, is known to cause ischemic necrosis in rats. Cardiotoxicity of three different doses of ISO were studied using physiological, biochemical and histopathological parameters. The effects of single and double dose of ISO were analysed, which illustrated that single ISO dose was more cardiotoxic than double ISO dose due to ischemic preconditioning. The tetrapeptide derivatives L-lysine-L-arginine-L-aspartic acid-L-serine (tetrapeptide A) and di-tert.butyloxycarbonyl-L-lysine-L-arginine-L-aspartic acid-tert.butyl O-tert.butyl-L-serinate (tetrapeptide B) along with acetylsalicylic acid as positive control were analysed at different time points for their cardioprotective effect. The results demonstrated that optimal protective effects were observed by pretreatment with 5 mg/kg of tetrapeptide B and this was found to be slightly better than that of acetylsalicylic acid. A lesser degree of cardioprotection was noticed when low doses of tetrapeptide B were administered. This study clearly showed that single dose of ISO (50 mg/kg, s.c.) induced myocardial necrosis could be used as a model to assess cardiovascular drugs and in this model, it was demonstrated that the tetrapeptide B could exhibit optimal cardioprotective effect.
盐酸异丙肾上腺素（ISO）是一种β肾上腺素能激动剂，已知会在大鼠中引起缺血性坏死。使用生理、生化和组织病理学参数研究了三种不同剂量ISO的心脏毒性。分析了单剂量和双剂量ISO的作用，结果表明由于缺血预处理，单剂量ISO比双剂量ISO的心脏毒性更大。在不同时间点分析了四肽衍生物L-赖氨酸-L-精氨酸-L-天冬氨酸-L-丝氨酸（四肽A）和二叔丁氧羰基-L-赖氨酸-L-精氨酸-L-天冬氨酸-叔丁基O-叔丁基-L-丝氨酸酯（四肽B）以及作为阳性对照的乙酰水杨酸的心脏保护作用。结果表明，用5mg/kg的四肽B预处理可观察到最佳保护效果，且发现其略优于乙酰水杨酸。给予低剂量四肽B时，观察到的心脏保护程度较低。本研究清楚地表明，单剂量ISO（50mg/kg，皮下注射）诱导的心肌坏死可作为评估心血管药物的模型，在该模型中，已证明四肽B可表现出最佳的心脏保护作用。
