Department of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Gifted and Talented Students Center, Iran University of Medical Sciences, Tehran, Iran.
Iran J Med Sci. 2021 Mar;46(2):136-143. doi: 10.30476/ijms.2019.82057.0.
Mebudipine, a dihydropyridine calcium-channel blocker (CCB), shows greater time- and voltage-dependent inhibitory effects than nifedipine. Its significant negative chronotropic effects without having considerable negative inotropic properties may make it a suitable candidate for the pharmacotherapy of heart failure (HF). This study aimed to investigate the possible beneficial action of mebudipine in a rat model of HF.
The present study carried out in the Department of Pharmacology at the Iran University of Medical Sciences during the years of 2009-2011. An experimental model of HF was induced in male Wistar rats using doxorubicin (DOX). The rats were divided into five groups with seven animals in each group: normal control group, DOX-induced HF control groups, and treatment groups. The animals were administered DOX for 15 days. A consistent deterioration occurred after a four-week rest period. The animals were then treated with intraperitoneal mebudipine (0.5 mg/kg) and intraperitoneal amlodipine (0.35 mg/kg), as well as an equal volume of distilled water for 15 days. The plasma levels of big endothelin-1 (BET-1), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as the clinical status (heart rate and blood pressure), were assessed before and after treatment. Statistical analysis was performed with SPSS software using parametric and nonparametric ANOVA.
Mebudipine and amlodipine reversed the increased plasma BET-1 values in the treated animals when compared with the HF control group (0.103 and 0.112 vs 0.231 pg/mL, respectively). The increased plasma levels of AST, ALT, CK-MB, and LDH were also reversed in the HF animals that received mebudipine or amlodipine.
The administration of mebudipine to HF animals, akin to amlodipine, palliated the clinical and biochemical signs of the disease in the present study. The abstract was presented in the Iranian Congress of Physiology and Pharmacology as a poster and published in the Scientific Information Database as a supplement (2015; Vol 22).
米贝地尔是一种二氢吡啶钙通道阻滞剂（CCB），与硝苯地平相比，它具有更强的时间和电压依赖性抑制作用。其显著的负变时作用而没有明显的负肌力作用，可能使它成为心力衰竭（HF）药物治疗的合适候选药物。本研究旨在探讨米贝地尔在 HF 大鼠模型中的可能有益作用。
本研究于 2009-2011 年在伊朗医科大学药理学系进行。使用阿霉素（DOX）诱导雄性 Wistar 大鼠建立 HF 实验模型。将大鼠分为五组，每组 7 只：正常对照组、DOX 诱导的 HF 对照组和治疗组。动物连续给药 15 天。在四周的休息期后，病情持续恶化。然后，动物连续 15 天腹腔内给予米贝地尔（0.5mg/kg）和氨氯地平（0.35mg/kg），以及等体积的蒸馏水。治疗前后评估大鼠血浆大内皮素-1（BET-1）、肌酸激酶心肌带（CK-MB）、乳酸脱氢酶（LDH）、天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平以及临床状态（心率和血压）。使用 SPSS 软件进行统计分析，采用参数和非参数 ANOVA。
与 HF 对照组相比，米贝地尔和氨氯地平逆转了治疗动物血浆 BET-1 值的升高（分别为 0.103 和 0.112 对 0.231pg/mL）。米贝地尔和氨氯地平也逆转了 HF 动物中升高的血浆 AST、ALT、CK-MB 和 LDH 水平。
在本研究中，米贝地尔给药 HF 动物，类似于氨氯地平，缓解了疾病的临床和生化征象。摘要作为海报在伊朗生理学和药理学大会上发表，并在科学信息数据库中作为增刊发表（2015 年；第 22 卷）。
