首页   按字顺浏览 期刊浏览 卷期浏览 CENTRAL CARDIOVASCULAR ACTIONS OF CALCIUM CHANNEL ANTAGONISTS IN DOGS
CENTRAL CARDIOVASCULAR ACTIONS OF CALCIUM CHANNEL ANTAGONISTS IN DOGS

 

作者: C. DAMASE‐MICHEL,   J.L. MONTASTRUC,   P. MONTASTRUC,  

 

期刊: Fundamental&Clinical Pharmacology  (WILEY Available online 1989)
卷期: Volume 3, issue S1  

页码: 57-64

 

ISSN:0767-3981

 

年代: 1989

 

DOI:10.1111/j.1472-8206.1989.tb00475.x

 

出版商: Blackwell Publishing Ltd

 

关键词: nicardipine;nifedipine;verapamil;diltiazem;sinoaortic denervation;central vascular regulation

 

数据来源: WILEY

 

摘要:

Summary—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 tachycardia due to baroreflex activation. By contrast, central (in‐tracisternal: 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 dener‐vated (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. Moreover, the magnitude of this sympathoexcitatory effect seems to vary according to the CCA group (phenylalkylamines being less potent that dihydropyridines) and to depend on the level of sympathetic tone: CCA exert stimulant effects when the sympathetic tone is low (normal dogs) and depressor actions when it

 

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