Endogenous nitrosyl factors may inhibit the desensitization of 5-HT3 receptors on vagal cardiopulmonary afferents

Joy A Owen; James N Bates; Stephen J Lewis

doi:10.1016/j.brainres.2005.08.023

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Endogenous nitrosyl factors may inhibit the desensitization of 5-HT3 receptors on vagal cardiopulmonary afferents

Journal article

Peer reviewed

Endogenous nitrosyl factors may inhibit the desensitization of 5-HT3 receptors on vagal cardiopulmonary afferents

Joy A Owen, James N Bates and Stephen J Lewis

Brain research, Vol.1059(2), pp.167-172

10/19/2005

DOI: 10.1016/j.brainres.2005.08.023

PMID: 16185669

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Abstract

The pronounced tachyphylaxis to the Bezold-Jarisch reflex (BJR) responses elicited by systemic injections of the 5-HT(3) receptor (5-HT(3)R) agonists such as phenylbiguanide (PBG) may involve desensitization and/or reduced rate of resensitization of 5-HT(3)Rs on vagal cardiopulmonary afferents. The presence of nitric oxide synthase (NOS) in vagal afferents raises the possibility that endogenous nitrosyl factors regulate the status of 5-HT(3)Rs in these afferents. Accordingly, the aim of this study was to determine whether the inhibition of NOS alters the development of tachyphylaxis to the BJR responses elicited by PBG in conscious rats. The first injection of PBG (100 microg/kg, i.v.) elicited robust reductions in heart rate (HR), diastolic arterial blood pressure (BP(D)), and cardiac output (CO) but minor changes in total peripheral resistance in saline-treated rats. Subsequent injections elicited progressively smaller responses such that the sixth injections elicited minor responses only. The first injection of PBG (100 microg/kg, i.v.) in rats treated with the NOS inhibitor, L-NAME (25 micromol/kg, i.v.) elicited similar reductions in HR, BP(D), and CO as in saline-treated rats. However, the rate of development of tachyphylaxis to PBG was markedly faster in the L-NAME-treated rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were markedly attenuated after the development of tachyphylaxis to PBG in saline- and in L-NAME-treated rats whereas the BJR responses elicited by the S-nitrosothiol, L-S-nitrosocysteine (5 micromol/kg, i.v.), were not attenuated in either group. These findings suggest that tachyphylaxis to PBG was not due to the loss of central or efferent processing of the BJR. Taken together, these findings suggest NOS exists in vagal cardiopulmonary afferents mediating the BJR and that nitrosyl factors influence 5-HT(3)R function.

Adaptation, Physiological

Animals

Biguanides - administration & dosage

Blood Pressure - drug effects

Cardiac Output - drug effects

Down-Regulation

Drug Administration Schedule

Enzyme Inhibitors - pharmacology

Heart Rate - drug effects

Male

NG-Nitroarginine Methyl Ester - pharmacology

Nitric Oxide Synthase - drug effects

Nitric Oxide Synthase - metabolism

Nitrogen Oxides - metabolism

Rats

Rats, Wistar

Receptors, Serotonin, 5-HT3 - drug effects

Receptors, Serotonin, 5-HT3 - metabolism

Reflex - drug effects

Reflex - physiology

Serotonin Receptor Agonists - administration & dosage

Tachyphylaxis - physiology

Vagus Nerve - drug effects

Vagus Nerve - enzymology

Details

Title: Subtitle: Endogenous nitrosyl factors may inhibit the desensitization of 5-HT3 receptors on vagal cardiopulmonary afferents
Creators: Joy A Owen - Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, 30602-7389, USA
James N Bates - University of Iowa, Anesthesia
Stephen J Lewis - Case Western Reserve University
Resource Type: Journal article
Publication Details: Brain research, Vol.1059(2), pp.167-172
DOI: 10.1016/j.brainres.2005.08.023
PMID: 16185669
ISSN: 0006-8993
eISSN: 1872-6240
Language: English
Date published: 10/19/2005
Academic Unit: Anesthesia
Record Identifier: 9984424843302771

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