Dissociation between duration of plasma catecholamine and blood pressure responses to beta-adrenergic blockade in normotensive subjects during physical exercise

Abstract

The influence of acute and chronic treatment with the adrenergic beta-receptor blocking agent propranolol (P) on blood pressure (BP), heart rate (HR) and plasma catecholamine concentration (CA) was studied in 7 normotensive healthy volunteers, and in 5 normotensive patients with cardiac neurosis, at rest, during physical exercise and after sudden withdrawal of the drug. The first oral dose of P 120 mg as well as chronic treatment (3×80 mg/day for 3 months) caused a significant reduction in HR and supine BP. Resting values of CA were not changed. After sudden withdrawal of the long-term therapy with P, supine BP and HR returned to normal, and again, resting levels of CA remained unchanged. A physical exercise test, performed 2 1/2 days after withdrawal of the betablocker, was not indicative of a transient sympathetic hyper-response. Striking effects of the drug on CA were observed during acute and chronic treatment with P when physical exercise was performed (bicycle ergometer, 150 W). Exercise values of CA were about twice as high during P treatment as without the drug, when the exercise test was performed 2 h after the first oral dose. At the same time, however, exercise BP and HR were significantly reduced. Similar reactions during the exercise test were also seen during chronic treatment with P, when the test was performed 2 hours after the last dose of the drug. But, when the exercise test was undertaken during chronic treatment 8 h after drug intake, the drug effect on CA had disappeared, whereas the effects on BP and HR still were present. The dissociation during chronic treatment between the effect on the duration of plasma CA and that of the pharmacodynamic responses to beta-adrenergic blockade with P is the principal finding of the study. A hypothesis is offered for interpretation of the observations. The time interval between measurement of drug effect and drug intake must be carefully observed in assessing different or controversial drug responses.