Department of Pharmacodynamics, Medical University of Łódź, Muszyńskiego 1, PL 90-151 Łódź, Poland.
Pharmacol Rep. 2010 Jan-Feb;62(1):86-94. doi: 10.1016/s1734-1140(10)70245-0.
A growing body of evidence suggests that some drugs used in cardiovascular diseases may modulate the level of proinflammatory cytokines. In the present study we examined whether nebivolol, a third generation beta-adrenergic blocker, influences lipopolysaccharide (LPS)-induced serum concentrations of TNF-alpha, IL-1beta, and IL-6 in normotensive (WKY) and spontaneously hypertensive rats (SHR). Nebivolol (5 mg/kg and 10 mg/kg) or vehicle were administered by gavage once a day for 21 days. The drug (5 mg/kg and 10 mg/kg) did not modify LPS-stimulated serum concentrations of TNF-alpha, IL-1beta and IL-6 in normotensive or hypertensive rats and did not affect the total cholesterol and HDL cholesterol level. Nebivolol, at the dose of 10 mg/kg, significantly increased the triglyceride concentration in SHR only. The results were accompanied by a statistically significant decrease in systolic, diastolic and mean blood pressure after 21 days of both of the drug doses. In hypertensive and normotensive rats, nebivolol had a hypotensive activity and neutral effect on lipid profile. In our in vivo model, the immunomodulating effect of the drug was not significant and probably did not depend on hemodynamic action.
越来越多的证据表明,一些用于心血管疾病的药物可能调节促炎细胞因子的水平。在本研究中,我们研究了第三代β肾上腺素能阻滞剂奈必洛尔是否影响正常血压(WKY)和自发性高血压大鼠(SHR)中脂多糖(LPS)诱导的血清 TNF-α、IL-1β 和 IL-6 浓度。奈必洛尔(5mg/kg 和 10mg/kg)或载体通过灌胃每天给药一次,共 21 天。该药物(5mg/kg 和 10mg/kg)未改变正常血压或高血压大鼠中 LPS 刺激的血清 TNF-α、IL-1β 和 IL-6 浓度,也不影响总胆固醇和高密度脂蛋白胆固醇水平。奈必洛尔(10mg/kg)剂量仅显著增加 SHR 的甘油三酯浓度。结果伴随着两种药物剂量给药 21 天后收缩压、舒张压和平均血压的统计学显著降低。在高血压和正常血压大鼠中,奈必洛尔具有降压活性和对脂质谱的中性作用。在我们的体内模型中,药物的免疫调节作用不显著,可能不依赖于血流动力学作用。