Central cardiovascular actions of calcium channel antagonists in dogs

Abstract

Several pharmacological and clinical studies have suggested that calcium channel antagonists (CCA) can exert central actions. The aim of the present study was to investigate their putative central cardiovascular properties in dogs. In normotensive pentobarbital-anesthetized dogs, intravenous (I.V.) nicardipine, -nifedipine -verapamil or diltiazem-induced a dose-dependent decrease in systolic and diastolic blood pressures followed by tachcardia due to baroreflex activation. By contrast, central (intracisternal: I.C.) administration of the same CCA (at doses ineffective by the I.V. route) induced an increase in both blood pressure and heart rate. Two kinds of neurogenic hypertensive sinoaortic denervated (SAD) dogs were used to study whether the central sympathoexcitatory effects of CCA depend on the level of the sympathetic tone. In acute SAD dogs (where the sympathetic tone is nearly maximum), I.V. administration of nicardipine, nifedipine, verapamil or diltiazem significantly reduced the SAD-induced increase in blood pressure and heart rate, thus demonstrating the sympathoinhibitory properties of CCA when sympathetic tone is maximum. In chronic SAD awake dogs (where the sympathetic tone is high but not maximum), I.V. nicardipine significantly decreased arterial blood pressure, but also induced both a marked tachycardia and a significant increase in plasma noradrenaline and adrenaline release. However, this direct central activation was not observed with verapamil I.V. under the same experimental conditions (chronic SAD awake dogs). The present data show that CCA could exert central cardiovascular actions in dogs. The positive chronotropic effects of CCA not only result from a baroreflex activation (following the decrease in blood pressure) but also from a direct centrally-mediated effect on sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)