Hemodynamic and metabolic effects of intravenous clentiazem in hypertensive patients

Abstract

To determine the hemodynamic and certain metabolic effects of clentiazem, a diltiazem congener, 10 untreated essential hypertensive patients were given the calcium antagonist in 3 successive doses totaling 1.0 mg/kg intravenously. Mean arterial pressure and total peripheral resistance progressively declined from 121 ± 3 mm Hg and 47 ± 2 U (mean) to 110 ± 3 mm Hg and 33 ± 1 U, respectively (p <0.05); heart rate remained unchanged. Cardiac output increased as a result of augmented cardiopulmonary volume (p <0.05) produced by peripheral venoconstriction and norepinephrine release (from 258 ± 41 to 319 ± 42 pg/ml; p <0.01). Surprisingly, there was an immediate reduction in plasma aldosterone (10.4 ± 1.2 to 6.5 ± 1.0 ng/dl; p <0.01), serum potassium (4.3 ± 0.1 to 3.6 ± 0.1 mEq/dl; p <0.001) and calcium (9.5 ± 0.1 to 8.8 ± 0.1 mg/dl; p <0.001) concentrations, whereas epinephrine increased (21.2 ± 3.3 to 45.8 ± 5.9 pg/ml; p <0.002). Previous studies with diltiazem, conducted similarly, did not show these changes. Therefore, clentiazem reduced mean arterial pressure through a decrease in total peripheral resistance, and released epinephrine was associated with intracellular potassium influx (urinary potassium did not change). The inhibited aldosterone release was not compensated by altered renal blood flow, glomerular filtration or increased plasma renin activity. These findings underscore the concept that calcium antagonists are a remarkably heterogeneous antihypertensive group.