Potassium disposition and neuroendocrine effects of propranolol, methyldopa and clonidine during dynamic exercise

In order to determine the changes in potassium disposition with antirenin, antihypertensives during dynamic physical activity, a double-blind placebo controlled study was undertaken using normal volunteers receiving placebo or single and multiple dose clonidine, methyldopa and propranolol 0.2 mg. followed by 0.1 mg. bid x 7 days, 500 mg. followed by 250 mg. bid x 7 days or 80 mg. followed by 40 mg. bid x 7 days, respectively. Prior to study, 2 hours post dosing and coincident with immediate pre-exercise on treadmill, at graded increases of exercise and 2 hours post exercise (approximately 4 hours post dosing), blood was sampled for potassium, renin concentration, aldosterone and catecholamines. Blood pressure (BP) and heart rate (HR) were measured. The results demonstrate no greater increase in potassium over placebo with single or multiple dose clonidine or methyldopa. Following the initial dose of propranolol, 80 mg., there was a statistically greater rise in potassium over that seen with placebo but not observed with multiple dose. This may be related to the low multiple dose regimen. There were minor but significant changes in norepinephrine, renin and systolic pressure with multiple dose clonidine and methyldopa and in renin, heart rate and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses, to exercise with methyldopa and propranolol are more biochemically altered than functionally impaired, yet the latter is related to dose and the underlying age and state of health of the group being studied.