In vitro and in vivo activities of anticholinergics on the cholinoceptors of the cardiac pacemaker cells

Journal of Autonomic Pharmacology

Breysse

et al. 1992

1. The cardiac cholinergic blockade and the chronotropic effect of the widely differing antimuscarinic drugs atropine and pirenzepine were investigated in the dog. 2. In conscious dogs, suppression of the parasympathetic system with atropine (0.2 mg kg-1 h-1) causes marked brief cardioacceleration (234 +/- 13 beats min-1) while pirenzepine (3 mg kg-1 h-1) causes moderate but persistent cardioacceleration (179 +/- 13 beats min-1). After suppression of the influence of the cardiac sympathetic system these cardioaccelerator effects are attenuated, particularly those of pirenzepine. 3. The effects of vagal stimulation are blocked completely and persistently by both agents. 4. When the cardioinhibitory action of the vagus nerve is blocked by pirenzepine the induced tachycardia can be increased by atropine, which causes an additional cardioacceleration (25 +/- 9 beats min-1). 5. These results show that the tachycardia induced by antimuscarinic agents is not only due to vagal blockade. The different mechanisms which may be involved are discussed. The results suggest that pirenzepine can suppress cholinergic influence on the heart more electively than atropine, which induced an 'excess tachycardia'. Also, intrinsic heart rate can be approached more closely when pirenzepine is used to suppress the parasympathetic system, than with atropine.

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Contribution of vagal blockade to the tachycardia induced by the antimuscarinic agents atropine and pirenzepine

Chassaing

Journal of Autonomic Pharmacology

Breysse

et al. 1992

Mechanisms of chronotropic cardiac effects of alinidine and plasma concentration-response relationships in the conscious dog with chronic atrioventricular block

Naunyn-Schmiedeberg's Arch Pharmacol

Chapuy

Lefebvre³

et al. 1989

The chronotropic cardiac effects of alinidine were studied in the conscious dog with chronic atrioventricular block. Alinidine at 0.5 - 4 mg/kg, i.e., at plasma concentrations between 42 +/- 2 and 1625 +/- 371 ng/ml, initially increased atrial rate dose-dependently. This effect fell off rapidly, but atrial bradycardia was never observed. After atropine and pindolol, which raised basal atrial rate, alinidine (2 mg/kg) decreased atrial rate, whereas after phenoxy-benzamine, yohimbine or phentolamine, it produced atrial effects identical to those observed under basal conditions, i.e., initial tachycardia and no bradycardia. Alinidine dose-relatedly decreased ventricular rate. None of the pretreatments modified the maximal ventricular bradycardia, but interestingly after pindolol or yohimbine this effect developed more rapidly (maximal bradycardia between 3 and 5 against 30 min) and then declined progressively. Alinidine did not modify mean blood pressure at any dose. After atropine, phenoxybenzamine or phentolamine, alinidine remained without effect on mean blood pressure, but after pindolol or yohimbine, a hypotensive effect appeared concomitantly with the reduction of the ventricular bradycardia. These results show that the initial atrial cardioacceleration due to alinidine results from a direct vagolytic action of this drug and that the absence of atrial bradycardia results from buffering by the vagolytic effect and/or a relatively low basal atrial rate. They also suggest that the ventricular bradycardia does not involve either the muscarinic cholinoceptors or the alpha- or beta-adrenoceptors, though the results obtained after pindolol or yohimbine suggest possible involvement of a fall in sympathetic tone by stimulation of presynaptic or central alpha2-adrenoceptors, particularly in the persistence of the bradycardic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine in the conscious dog with chronic heart-block

Naunyn-Schmiedeberg's Arch. Pharmacol.

Dubray

Duchêne-Marullaz

1984

The chronotropic effects of dopamine were studied in the conscious dog with chronic A-V block. Dopamine at 12.5-200 micrograms/kg and 12.5-50 micrograms/kg/min lowered atrial rate independently of dose. After blockade of muscarine receptors or alpha-adrenoceptors, it raised atrial rate. After blockade of dopamine receptors, dopamine still lowered atrial rate, and did so dose-relatedly after blockade of beta-adrenoceptors. It raised ventricular rate, and at high doses also induced ventricular rhythm disorders. Blockade of muscarine receptors enhanced the ventricular cardioaccelerator effect of dopamine (P less than 0.025) at 100 micrograms/kg, while blockade of alpha-adrenoceptors reduced it (P less than 0.05). Blockade of dopamine receptors did not modify this effect, but blockade of beta-adrenoceptors reversed it. Dopamine at 25-200 micrograms/kg raised mean blood pressure. This effect was enhanced by blockade of muscarine receptors, reversed by blockade of alpha-adrenoceptors, and was unaffected by blockade of beta-adrenoceptors or dopamine receptors. These results show that the atrial cardiomoderator effect of dopamine is a vagal reflex response to its hypertensive action, and that it is limited by its direct beta-adrenergic stimulating action. They also show that the ventricular cardioaccelerator effect of dopamine is attenuated by a reflex vagal depressor effect consequent to the induced hypertension. No evidence was found for the existence of positive chronotropic dopamine receptors in either atria or ventricles.