Central cardiovascular actions of calcium channel antagonists in dogs. 1989

C Damase-Michel, and J L Montastruc, and P Montastruc
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.

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)

UI MeSH Term Description Entries
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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