Andrzejczak Dariusz, Górska Dorota, Czarnecka Elzbieta
Department of Pharmacodynamics, Medical University of Łódź,, Muszyńskiego 1, PL 90-151 Łódź, Poland.
Pharmacol Rep. 2006 Sep-Oct;58(5):711-9.
An increasing body of evidence suggests that cytokines may play a role in the pathogenesis of cardiovascular diseases. Immunopharmacological studies provide new information on immunomodulating activity of some drugs, including their effect on the level of pro-inflammatory cytokines. The aim of the present study was to find out whether amlodipine and atenolol, drugs applied in the treatment of arterial hypertension, can modulate lipopolysaccharide (LPS)-induced pro-inflammatory cytokine level (TNF-alpha, IL-1, IL-6) in spontaneously hypertensive rats (SHR). The experiments were performed on 4 groups of animals as follows: WKY + MET(control Wistar-Kyoto normotensive rats), SHR + MET(control hypertensive rats), SHR + AML(hypertensive rats receiving amlodipine), SHR + AT (hypertensive rats receiving atenolol). Control rats received 1% solution of methylcellulose (1 ml/kg) by a gavage. Amlodipine and atenolol were administered by a gavage at doses of 15 mg/kg and 25 mg/kg, respectively. Arterial blood pressure was measured in conscious rats, using the tail-cuff method. Serum tumor necrosis factor alpha (TNF)-alpha, interleukin (IL)-1 and IL-6 concentrations were measured with enzyme-linked immunosorbent assay kits. Additionally, lipid levels were evaluated. The present data provide the evidence that amlodipine and atenolol act as immunomodulators of pro-inflammatory cytokines in SHR. Amlodipine decreased TNF-alpha, increased IL-6 and did not affect IL-1 level. Atenolol did not influence TNF-alpha and IL-1, but raised IL-6 in SHR. Additionally, amlodipine decreased total cholesterol level without changing HDL cholesterol level whereas atenolol did not influence lipid levels. The identification of additional immunomodulating properties of hypotensive drugs may be important for better understanding of their mechanisms of action.
越来越多的证据表明，细胞因子可能在心血管疾病的发病机制中起作用。免疫药理学研究提供了一些药物免疫调节活性的新信息，包括它们对促炎细胞因子水平的影响。本研究的目的是确定用于治疗动脉高血压的药物氨氯地平和阿替洛尔是否能调节自发性高血压大鼠（SHR）中脂多糖（LPS）诱导的促炎细胞因子水平（TNF-α、IL-1、IL-6）。实验在4组动物上进行，如下：WKY + MET（对照Wistar-Kyoto正常血压大鼠）、SHR + MET（对照高血压大鼠）、SHR + AML（接受氨氯地平的高血压大鼠）、SHR + AT（接受阿替洛尔的高血压大鼠）。对照大鼠通过灌胃给予1%甲基纤维素溶液（1 ml/kg）。氨氯地平和阿替洛尔分别以15 mg/kg和25 mg/kg的剂量通过灌胃给药。使用尾袖法在清醒大鼠中测量动脉血压。用酶联免疫吸附测定试剂盒测量血清肿瘤坏死因子α（TNF）-α、白细胞介素（IL）-1和IL-6浓度。此外，评估血脂水平。目前的数据证明氨氯地平和阿替洛尔在SHR中作为促炎细胞因子的免疫调节剂起作用。氨氯地平降低了TNF-α，升高了IL-6，并且不影响IL-1水平。阿替洛尔不影响TNF-α和IL-1，但升高了SHR中的IL-6。此外，氨氯地平降低了总胆固醇水平而不改变高密度脂蛋白胆固醇水平，而阿替洛尔不影响血脂水平。确定降压药物的其他免疫调节特性可能有助于更好地理解它们的作用机制。
