Hernández F T, Zapater P, De-Madaria E, Palazón J M, Pascual S, Irurzun J, Such J, Perez-Mateo M, Horga J F
Clinical Pharmacology Unit, Hospital General Universitario, and Departamento de Farmacología and Terapéutica, Facultad de Medicina, Universidad Miguel Hernández, San Juan de Alicante, Spain.
Vascul Pharmacol. 2006 Jun;44(6):464-8. doi: 10.1016/j.vph.2006.03.001. Epub 2006 Apr 19.
Propranolol is a widely used drug for prophylaxis of variceal bleeding in patients with cirrhosis, but not all patients show an adequate clinical response. This variability may be in relation to beta adrenoceptor activity, but no information is available in this setting. Thirty-nine patients with advanced cirrhosis and presence of oesophageal varices were sequentially included. We studied the function of beta-2-adrenoceptor in isolated membranes of mature erythrocytes obtained from patients by measuring cyclic AMP (cAMP) production before and after isoproterenol. Blood samples obtained from 11 healthy volunteers were used as control. Patients showed a six-fold increase in the mean basal cAMP production as compared to healthy volunteers. Isoproterenol produced a small, non-significantly and highly variable increase in the AC activity in patients compared with controls. cAMP values remain stable after three months of continuous treatment with oral beta-blockers in both groups. Patients without antecedent of variceal bleeding or with an active alcohol intake showed a significantly higher isoproterenol effect. In conclusion, beta-receptor function in human erythrocytes membranes is altered in patients with cirrhosis and oesophageal varices.
普萘洛尔是一种广泛用于预防肝硬化患者静脉曲张出血的药物,但并非所有患者都有足够的临床反应。这种变异性可能与β肾上腺素能受体活性有关,但在这种情况下尚无相关信息。我们依次纳入了39例晚期肝硬化且存在食管静脉曲张的患者。我们通过测量异丙肾上腺素前后的环磷酸腺苷(cAMP)生成量,研究了从患者获取的成熟红细胞分离膜中β2肾上腺素能受体的功能。从11名健康志愿者采集的血样用作对照。与健康志愿者相比,患者的平均基础cAMP生成量增加了6倍。与对照组相比,异丙肾上腺素使患者的腺苷酸环化酶(AC)活性有小幅、无显著差异且高度可变的增加。两组患者口服β受体阻滞剂连续治疗3个月后,cAMP值保持稳定。既往无静脉曲张出血史或有酒精摄入的患者,异丙肾上腺素的效应显著更高。总之,肝硬化和食管静脉曲张患者的人红细胞膜β受体功能发生了改变。