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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.
Johansson et al. (Fri,) studied this question.