Hemodynamic Effects and Power Spectral Analysis of Heart Rate and Arterial Pressure Variabilities Induced by Lercanidipine and Its Enantiomers in Conscious Dogs

Abstract

This study was performed to investigate the hemodynamic properties and to analyze the effects on spectral analysis indexes (LFRR, HFRR) of autonomic control of cardiovascular function induced by administration of lercanidipine and its enantiomers in conscious, instrumented dogs. After cumulative i.v. administration, lercanidipine and its (S)-enantiomer induced dose-dependent peripheral and coronary vasodilatation. Concomitant increases in dP/dtmax and cardiac output were observed. (S)-Lercanidipine modified hemodynamic parameters, paralleling the action of the racemate at half-dose. (R)-Lercanidipine was devoid of any vasodilating action. The effects of nitrendipine on peripheral and coronary vasculature were similar to those of lercanidipine but with a lesser increase of dP/dtmax compared to lercanidipine. Both (S)-lercanidipine and lercanidipine caused a significant increase in heart rate, but only (S)-lercanidipine significantly increased LFRR. The marker of vasomotor activity LFSAP showed a mild reduction after lercanidipine, suggesting the possibility of a blunting action on vasomotor sympathetic activity. After lercanidipine infusion at a dose of 1 μg/kg/min for 15 min, total peripheral resistance and coronary resistance decreased significantly, together with a corresponding increase in coronary blood flow. After β-adrenergic blockade with propranolol, its coronary effects were slightly reduced. The time relaxation constant TAU was not modified in both conditions. Continuous infusion of lercanidipine did not modify the spectral markers LFRR and LFSAP. Pretreatment with propranolol did not significantly alter the response to lercanidipine, thus confirming the virtual absence of sympathetic activation during continuous infusion. In conclusion, lercanidipine is confirmed to be a direct and potent vasodilator calciumentry blocker with selectivity for the vascular bed.