Böhlen L M, de Courten M, Hafezi F, Shaw S, Riesen W, Weidmann P
Medizinische Poliklinik, University of Berne, Switzerland.
J Cardiovasc Pharmacol. 1994 Jun;23(6):877-83. doi: 10.1097/00005344-199406000-00004.
beta-Receptor blockers may exert a spectrum of metabolic and humoral effects, which might differ depending on the specific adrenoreceptor characteristics of the individual agents. We investigated the influence of celiprolol, a beta 1-blocker with beta 2-agonistic and, possibly, additional weak alpha-receptor antagonistic properties, on insulin sensitivity (SI), glucose homeostasis, and lipid profile in 20 young, healthy, normotensive individuals. SI, fasting plasma glucose and insulin, serum total triglycerides (TG), lipoprotein cholesterol (C) fractions, lipoprotein a [Lp(a)], and plasma atrial natriuretic factor (ANF) levels were determined before and after acute glucose loading under placebo conditions and after 3 weeks of celiprolol administration. The participants were instructed to follow a 3-day standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% protein) and an overnight fast before measurements were recorded. As compared with control values, SI, fasting plasma glucose and insulin, the areas under the glucose and insulin curves, the k value of glucose disappearance after glucose load, and serum cholesterol fractions, TG, and Lp(a) were unchanged during celiprolol administration. However, celiprolol significantly reduced plasma ANF levels (p < 0.02). The latter increased in response to acute hyperglycemia/hyperinsulinemia with placebo (p < 0.05) but not with celiprolol. Although diastolic blood pressure (DBP) decreased slightly during the first and second week of celiprolol administration, BP and heart rate (HR) did not differ significantly after 3 weeks on celiprolol treatment as compared with placebo conditions. Our findings demonstrate that in healthy lean humans beta-receptor modulation with celiprolol is neutral with regard to SI and lipoprotein metabolism. Moreover, glucose loading stimulates whereas celiprolol decreases plasma ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)
β受体阻滞剂可能会产生一系列代谢和体液效应,具体效应可能因各药物的特定肾上腺素能受体特性而异。我们研究了具有β2激动及可能附加的微弱α受体拮抗特性的β1阻滞剂塞利洛尔,对20名年轻、健康、血压正常个体的胰岛素敏感性(SI)、葡萄糖稳态及血脂谱的影响。在安慰剂条件下急性葡萄糖负荷前后以及塞利洛尔给药3周后,测定SI、空腹血浆葡萄糖和胰岛素、血清总甘油三酯(TG)、脂蛋白胆固醇(C)组分、脂蛋白a[Lp(a)]以及血浆心房利钠因子(ANF)水平。在记录测量值之前,参与者被要求遵循3天标准饮食(2500千卡/天,45%碳水化合物,40%脂肪,15%蛋白质)并禁食过夜。与对照值相比,在塞利洛尔给药期间,SI、空腹血浆葡萄糖和胰岛素、葡萄糖和胰岛素曲线下面积、葡萄糖负荷后葡萄糖消失的k值以及血清胆固醇组分、TG和Lp(a)均未改变。然而,塞利洛尔显著降低了血浆ANF水平(p<0.02)。安慰剂情况下急性高血糖/高胰岛素血症会使后者升高(p<0.05),但塞利洛尔给药时则不然。虽然塞利洛尔给药的第一周和第二周舒张压(DBP)略有下降,但与安慰剂条件相比,塞利洛尔治疗3周后血压(BP)和心率(HR)并无显著差异。我们的研究结果表明,在健康瘦人身上,用塞利洛尔进行β受体调节对SI和脂蛋白代谢呈中性。此外,葡萄糖负荷会刺激而塞利洛尔会降低血浆ANF水平。(摘要截短于250字)