Hemodynamic effects of labetalol in young and elderly hypertensives during exercise and at rest

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Interdepartmental Studies

First Committee Member

Donald J. Weidler - Committee Chair


Labetalol is a combined alpha and beta adrenoceptor blocking agent. It is a nonselective competitive antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha-adrenoceptors. To understand the hemodynamic differences in blood pressure (BP) regulation in young (YH) and elderly hypertensives (EH), 8 YH, (35-54 years old) and 8 EH, (65-73 years old) were randomly enrolled in a placebo controlled double blind phase after a four-week single blind placebo treatment period. At the start of the six-day confinement period, the pre-treatment baseline (day 0) was established over a 24-hour period for the following parameters: BP, heart rate (HR), rate-pressure product (SBP x Hr), total peripheral resistance (TPR) plasma renin activity (PRA), aldosterone (ALD), creatinine clearance, urinary sodium and potassium, and echocardiography (left ventricle dimension, ejection fraction (EF), stroke volume (SV), cardiac output (CO)). These same parameters were measured after a single dose of 200 mg labetalol on day 1 (acute) and after multiple dosing on day 5 (chronic). All patients were subjected to a multistage treadmill exercise tolerance test at the estimated maximum plasma concentration of labetalol. In all patients, labetalol promptly and significantly reduced BP (supine and standing) without significantly reducing HR. This decrease was greater in the erect position than in the supine position. There were not significant changes in the CO and SV. The YH and EH demonstrated that labetalol did not have an effect on the indices of left ventricular function, nor were significant differences detected between patient groups. Labetalol significantly reduced TPR and mean BP at exercise baseline after both acute and chronic administration. This decline was accompanied by significant decrease in myocardial oxygen demand. EH who were treated with labetalol had an increase in exercise duration, and there was no apparent training effect; the rate-pressure product, systolic and diastolic BP responses to exercise were significantly blunted. Labetalol appears to have no detrimental effect on the renal function of the EH group. Labetalol appears to be well tolerated and was found to be an effective monotherapy in the EH group; it was devoid of the adverse effects generally associated with pure beta-blocking drugs. (Abstract shortened with permission of author.)


Health Sciences, Pharmacology

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