Naloxone-induced potentiation of cardiac alpha-2 adrenoceptor-mediated depression of neurogenic tachycardia

Document Type

Article

Publication Date

1993

Abstract

The objective of this investigation was to test the hypothesis that naloxone directly activates alpha-2 adrenoceptors to cause depression of neurogenic tachycardia as suggested in an earlier investigation (Naloxone- Induced Bradycardia in Pithed Rats: Evidence for an Interaction with the Peripheral Sympathetic Nervous System and Alpha-2 Adrenoceptors. J. Pharmacol. Exp. Ther. 296:916-926, 1992). Bolus doses of naloxone in a range of 10-1000 μg/kg i.v., administered in the presence of sustained neurogenic tachycardia (108 ± 10 beats per min), resulted in a dose-dependent inhibition of neurogenic tachycardia with a maximum inhibitory response of 21% and an ED50 of 55 ± 2.3 μg/kg. The inhibition of the naloxone- induced inhibition of neurogenic tachycardia was antagonized by phentolamine (5 mg/kg i.v.) and rauwolscine (0.5 mg/kg i.v.), but not prazosin (0.1 mg/kg i.v.). In the absence of sympathetic nerve activity, low doses of naloxone (10-300 μg/kg i.v.) had no effect on heart rate. These data suggest that naloxone in lower doses (10-1000 μg/kg i.v.) is a partial agonist at prejunctional alpha-2 adrenoceptors. In the presence of a steady-state maximum response (21% inhibition of neurogenic tachycardia) caused by naloxone infusion (100 and 1000 μg/kg/min i.v.), the ED50 of the preferential alpha-2 adrenoceptor agonist, UK14304-18, was not shifted to the right, but instead shifted to the left. This suggests that naloxone-induced depression of the neurogenic tachycardia does not involve the direct activation of alpha-2 adrenoceptors, but involves the potentiation of alpha- 2 adrenoceptor-mediated inhibition of heart rate through an unknown mechanism.

Publication Title

Journal of Pharmacology and Experimental Therapeutics

Volume

266

Issue

1

First Page

184

Last Page

191

Comments

This article was published in Journal of Pharmacology and Experimental Therapeutics, Volume 266, Issue 1, Pages 184-191.

The published version is available at http://jpet.aspetjournals.org/ .

Copyright © 1993.

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