Aging and cardiovascular responsiveness to β‐agonist in humans: Role of changes in β‐receptor responses versus baroreflex activity

Objectives To assess age‐related changes in the cardiac chronotropic and inotropic responses and arterial responses to β‐receptor stimulation and the potential role of the arterial baroreflex on these responses. Methods and Results Isoproterenol alone was infused in 14 young subjects (age, 30 ± 2 years) and 15 older healthy volunteers (age, 60 ± 2 years) and together with ganglionic blockade (trimethaphan) in eight young and eight older subjects. Isoproterenol was infused at 3 to 4 incremental rates. Cardiac function was assessed by echocardiography and peripheral arterial responses were measured by venous occlusion plethysmography. Before ganglionic blockade, isoproterenol at infusion rates from 0.005 to 0.03 µg/kg/min caused similar changes in heart rate, ejection fraction, and mean normalized systolic ejection rate in the young and older subjects. With concomitant use of trimethaphan, isoproterenol at infusion rates from 0.0025 to 0.01 µg/kg/min caused in young subjects a larger increase in heart rate (29 ± 2 beats/min [young] versus 20 ± 3 [older] at peak infusion; p = 0.03), ejection fraction (11% ± 2% [young] versus 6% ± 1% [older]; p < 0.01), and mean normalized systolic ejection rate (1.13 ± 0.2 ml/sec [young] versus 0.48 ± 0.09 [older]; p < 0.01). Whereas percentage changes in total peripheral resistance were larger in the young subjects, there were no significant age‐related differences in the responses of forearm blood flow and resistance before or after ganglionic blockade. Conclusions These results indicate an age‐related decrease in β‐receptor responsiveness of both sinoatrial node and ventricular myocardium that is masked by a concomitant decrease in the baroreflex control of the heart. Clinical Pharmacology and Therapeutics (1994) 56, 543–553; doi: 10.1038/clpt.1994.176