Department of Pharmacodynamics, Medical University of Lodz, Lodz, Poland.
Department of Pharmacodynamics, Medical University of Lodz, Lodz, Poland.
Pharmacol Rep. 2014 Feb;66(1):68-73. doi: 10.1016/j.pharep.2013.08.006. Epub 2014 Feb 1.
A growing body of evidence suggests that some cardiovascular drugs could modulate the level of proinflammatory cytokines. Therefore, the aim of the present study was to investigate whether celiprolol, a third generation β-adrenoceptor blocker, affects lipopolysaccharide (LPS)-induced serum concentrations of TNF-α, IL-1β, IL-6 in normotensive (WKY) and spontaneously hypertensive (SHR) rats.
Celiprolol (150 mgkg(-1)) or vehicle was administered by gavage once daily for 21 days. Arterial blood pressure was measured in conscious rats, using the tail-cuff method. Serum concentrations of proinflammatory cytokines were measured with enzyme-linked immunosorbent assay kits. Additionally, plasma concentrations of total cholesterol, HDL-cholesterol and triglycerides were evaluated.
In normotensive WKY rats celiprolol did not affect heart rate, blood pressure, or the serum concentrations of triglycerides, total cholesterol or HDL-cholesterol. In hypertensive animals the drug decreased lipid parameters, increased diastolic and mean blood pressure after the first week of administration, and produced a small but significant decrease in heart rate after the first two weeks of the treatment. In both groups of animals, celiprolol decreased LPS-stimulated serum concentration of IL-6 but did not affect levels of TNF-α and IL-1β.
It is suggested that the IL-6-modulating properties of celiprolol could provide additional value to the therapeutic effectiveness of the drug in the treatment of hypertension.
越来越多的证据表明，一些心血管药物可以调节促炎细胞因子的水平。因此，本研究旨在探讨第三代β肾上腺素受体阻滞剂塞利洛尔是否影响正常血压（WKY）和自发性高血压（SHR）大鼠脂多糖（LPS）诱导的血清 TNF-α、IL-1β、IL-6 浓度。
塞利洛尔（150mgkg(-1)）或载体通过灌胃每天一次给药 21 天。使用尾套法在清醒大鼠中测量动脉血压。通过酶联免疫吸附测定试剂盒测量促炎细胞因子的血清浓度。此外，评估了总胆固醇、HDL-胆固醇和甘油三酯的血浆浓度。
在正常血压的 WKY 大鼠中，塞利洛尔不影响心率、血压或甘油三酯、总胆固醇或 HDL-胆固醇的血清浓度。在高血压动物中，该药物降低了脂质参数，在给药第一周后增加了舒张压和平均血压，并在治疗的前两周后使心率略有但显著降低。在两组动物中，塞利洛尔均降低了 LPS 刺激的血清 IL-6 浓度，但不影响 TNF-α和 IL-1β的水平。
塞利洛尔调节 IL-6 的特性可能为该药物在治疗高血压方面的治疗效果提供额外的价值。
