Johansson S R, Hjalmarson A
Department of Medicine I, Sahlgren's Hospital, University of Gothenburg, Sweden.
Scand J Clin Lab Invest. 1988 Apr;48(2):183-91. doi: 10.3109/00365518809085411.
Dose-response curves for intravenous bolus injections of isoprenaline were carried out in 40 normal subjects, in four groups of 10 comprising young and middle-aged males and females. The isoprenaline dose required to raise the heart rate by 50 beats/min, the CD50 (chronotropic dose 50 beats/min), was calculated individually and taken as a measure of the beta-adrenergic responsiveness. Females had significantly higher sensitivity to isoprenaline than males, i.e. lower CD50 values (95% confidence interval 0.07-0.11 versus 0.12-0.17 micrograms/kg body weight, p less than 0.001), and young subjects had higher sensitivity than middle-aged subjects (95% confidence interval for CD50 0.07-0.10 versus 0.12-0.18 microgram/kg body weight, p less than 0.001). Dose-response curves were also carried out for intravenous prenalterol, a partial beta 1-adrenergic agonist. The maximal heart-rate response to prenalterol (delta HRP) showed a significant inverse linear relationship with the CD50 (delta HRP = 44.8-0.11 x CD50, r = -0.53, rs = -0.69, p less than 0.001). A mental stress programme and isometric exercise gave significant increases in heart rate and blood pressure for all groups, but there was no significant relationship between the CD50 and the heart-rate response. By applying a theoretical model, developed by Kenakin and Beek [13], to the isoprenaline-prenalterol data, it is suggested that the observed age and sex differences in beta-adrenergic responsiveness are caused by a tissue-related difference in the stimulus-response mechanism.
对40名正常受试者进行了静脉推注异丙肾上腺素的剂量反应曲线实验,受试者分为四组,每组10人,包括青年和中年男性及女性。计算出使心率提高50次/分钟所需的异丙肾上腺素剂量,即CD50(变时剂量50次/分钟),并将其作为β-肾上腺素能反应性的一种衡量指标。女性对异丙肾上腺素的敏感性显著高于男性,即CD50值较低(95%置信区间为0.07 - 0.11微克/千克体重,而男性为0.12 - 0.17微克/千克体重,p < 0.001),且青年受试者的敏感性高于中年受试者(CD50的95%置信区间为0.07 - 0.10微克/千克体重,而中年受试者为0.12 - 0.18微克/千克体重,p < 0.001)。还对静脉注射普瑞特罗(一种部分β1-肾上腺素能激动剂)进行了剂量反应曲线实验。普瑞特罗引起的最大心率反应(δHRP)与CD50呈显著的负线性关系(δHRP = 44.8 - 0.11×CD50,r = -0.53,rs = -0.69,p < 0.001)。心理应激程序和等长运动使所有组的心率和血压显著升高,但CD50与心率反应之间无显著关系。通过将Kenakin和Beek [13]开发的理论模型应用于异丙肾上腺素 - 普瑞特罗数据,提示观察到的β-肾上腺素能反应性的年龄和性别差异是由刺激 - 反应机制中与组织相关的差异引起的。