Analysis of mechanisms responsible for the bradycardic action of naloxone after haemorrhage in the conscious rabbit.

We have analyzed the efferent mechanisms responsible for the bradycardia that occurs when naloxone (6 mg/kg) is given i.v. to conscious rabbits after acute blood loss of 17-20 ml/kg. Atenolol and hyoscine methyl bromide were given intrapericardially (i.p.c.), singly and in combination, to allow factorial analysis of the contributions of sympathoadrenal beta-adrenergic and vagal cholinergic mechanisms. In addition, the effects of ganglion blockade with mecamylamine on the heart rate response to naloxone, and of i.p.c. naloxone on the cardiac pacemaker, were tested. The treatments had little effect on the pressor response to naloxone. Central nervous mechanisms were responsible for most of the bradycardia of approximately 160 beats/min evoked by naloxone in sham-treated, bled, rabbits. Increased vagal drive accounted for one-half the response, withdrawal of sympathoadrenal drive for 20%, and there was no significant interaction. These effects appeared to be due to evocation of a baroreceptor-heart rate reflex by the concomitant rise in blood pressure. Non-cholinergic, non-adrenergic mechanisms were responsible for a fall in heart rate of approximately 35 beats/min, part of which was due to a direct action of naloxone on the cardiac pacemaker.