选择性β_1受体阻滞剂对高血压病患者β受体亚型功能的调节特性

Regulative characteristics of β-adrenoreceptor subtypal function in patients with essential hypertension by chronic β_1 selective antagonist

目的探讨选择性β１受体阻滞剂对人体心肌β受体亚型功能的影响。方法采用踏车运动法与羟甲叔丁肾上腺素药物试验，测定２０例连续接受选择性β１受体阻滞剂治疗４个月以上的高血压病男性患者，停药后３天峰运动功率心率最大增加值（β１受体反应性）与羟甲叔丁肾上腺素（选择性β２受体激动剂）增加心率３０次／分的变时剂量（ＣＤ３０，β２受体反应性）；２０例至少４个月内未服用β受体阻滞剂的高血压病男性患者予以同期测定，以作对照。结果峰运动功率心率最大增加值选择性β１受体阻滞剂治疗组为８８．１±１０．５次／分，比非β受体阻滞剂治疗组（７８．５±９．４次／分）无明显差异（Ｐ＞０．０５）；静脉注射羟甲叔丁肾上腺素ＣＤ３０选择性β１受体阻滞剂治疗组为１．８±０．３μｇ／ｋｇ，比非β受体阻滞剂治疗组（２．７±０．２μｇ／ｋｇ）显著降低（Ｐ＜０．００１）。结论选择性β１受体阻滞剂具有交叉选择性提高心肌β２受体功能的生物学特性，这可能是β受体阻滞剂停药综合征的细胞学机制。

Objective To study the effect of chronic β 1 selective blockor treatment on β adrenoreceptor subtypal function in human. Methods Cardiac β 1 adrenoreceptor subtypes responsiveness were measured by treadmill exercise test and cardiac β 2 adrenoreceptor responsiveness by salbutamol injection test in 20 male patients with essential hypertension (EH) after β 1 selective blockor treatment for at least 4 months and withdrawal for 3 days. The twenty male patients with EH and non β blockors treatment for at least 4 months were used as controls. Results The increases in peak exercise heart rate by treadmill were not significantly different between the patients with β 1 blockor treatment and those with non β blockor treatment. The chronotropic dose of salbutamol that increased heart rate by 30 beats/min [chronotropic dose 30 (CD 30 )] in β 1 blockor treatment group were significantly lower than those in non β blockor treatment group (1.8±0.3 vs 2.7±0.2 μg/kg, P <0.001). Blood pressures did not change significantly after salbutamol injection in both groups. Conclusion The treatment with β 1 selective blockor leads to cross sensitisation of cardiac β 2 adrenoreceptor in human. This is the possible celluological mechanism of the β blockor withdrawal syndrome.