Age and sex differences in cardiovascular reactivity to adrenergic agonists, mental stress and isometric exercise in normal subjects

Abstract

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 β-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 μg/kg body weight, p<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 μg/kg body weight, p<0.001). Dose-response curves were also carried out for intravenous prenalterol, a partial β₁-adrenergic agonist. The maximal heart-rate response to prenalterol (ΔHRP) showed a significant inverse linear relationship with the CD₅₀, (ΔHRp=44.8-0.11×CD₅₀, r=-0.53, r_s=-0.69, p<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 β-adrenergic responsiveness are caused by a tissue-related difference in the stimulus-response mechanism.

Key Words:

• adrenergic age difference
• adrenergic sex difference
• chronotropic dose 50
• isoprenaline
• prenalterol