Veeraveedu Punniyakoti T, Watanabe Kenichi, Ma Meilei, Gurusamy Narasimman, Palaniyandi Suresh S, Wen Juan, Prakash Paras, Wahed Mir Imam Ibne, Kamal Fadia A, Mito Sayaka, Kunisaki Megumi, Kodama Makoto, Aizawa Yoshifusa
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Pharmacology. 2006;77(1):1-10. doi: 10.1159/000091746. Epub 2006 Feb 27.
The aim of the present study was to compare the cardioprotective properties of long-acting calcium channel antagonist pranidipine with amlodipine in rat model of heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were randomized for the oral administration of low-dose amlodipine (1 mg/kg/day), high-dose amlodipine (5 mg/kg/day), pranidipine (0.3 mg/kg/day) or vehicle (0.5% methylcellulose). After oral administration for 1 month, the animals underwent echocardiography and hemodynamic analysis. Histopathology, immunohistochemistry, and Western immunoblotting were carried out in the heart samples. Both pranidipine and high-dose amlodipine increased survival rate. Although the heart rate did not differ among the four groups, left ventricular end-diastolic pressure was significantly decreased and +/-dP/dt was increased in the pranidipine- and high-dose amlodipine-treated rats, but not in low-dose amlodipine-treated rats. In comparison to amlodipine treatment, pranidipine treatment significantly reduced myocyte size and central venous pressure. Furthermore, both pranidipine and high-dose amlodipine treatment significantly reduced myocardial protein levels of atrial natriuretic peptide and inducible nitric oxide synthase, whereas pranidipine only significantly decreased tumor necrosis factor-alpha, and improved sarcoplasmic reticulum Ca2+ ATPase2 protein levels. We conclude that pranidipine ameliorates the progression of left ventricular dysfunction and cardiac remodeling in rats with heart failure after autoimmune myocarditis in a lower dose when compared to amlodipine and which may be a clinically potential therapeutic agent for the treatment of heart failure.
本研究的目的是在自身免疫性心肌炎诱导的大鼠心力衰竭模型中，比较长效钙通道拮抗剂普拉地平与氨氯地平的心脏保护特性。免疫后28天，将存活的大鼠随机分组，分别口服低剂量氨氯地平（1毫克/千克/天）、高剂量氨氯地平（5毫克/千克/天）、普拉地平（0.3毫克/千克/天）或赋形剂（0.5%甲基纤维素）。口服给药1个月后，对动物进行超声心动图和血流动力学分析。对心脏样本进行组织病理学、免疫组织化学和蛋白质免疫印迹分析。普拉地平和高剂量氨氯地平均提高了存活率。虽然四组之间心率无差异，但普拉地平和高剂量氨氯地平治疗的大鼠左心室舒张末期压力显著降低，±dP/dt升高，而低剂量氨氯地平治疗的大鼠则无此现象。与氨氯地平治疗相比，普拉地平治疗显著减小了心肌细胞大小并降低了中心静脉压。此外，普拉地平和高剂量氨氯地平治疗均显著降低了心房利钠肽和诱导型一氧化氮合酶的心肌蛋白水平，而普拉地平仅显著降低了肿瘤坏死因子-α，并改善了肌浆网Ca2+ATPase2蛋白水平。我们得出结论，与氨氯地平相比，普拉地平以较低剂量改善了自身免疫性心肌炎后心力衰竭大鼠左心室功能障碍和心脏重塑的进展，可能是治疗心力衰竭的一种具有临床潜力的治疗药物。
