Intracellular cGMP may promote Ca2+-dependent and Ca2+-independent release of catecholamines from sympathetic nerve terminals

Erin J Whalen; Timothy B Saurer; Alan Kim Johnson; Stephen J Lewis

doi:10.1016/j.vph.2006.03.006

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Intracellular cGMP may promote Ca2+-dependent and Ca2+-independent release of catecholamines from sympathetic nerve terminals

Journal article

Peer reviewed

Intracellular cGMP may promote Ca2+-dependent and Ca2+-independent release of catecholamines from sympathetic nerve terminals

Erin J Whalen, Timothy B Saurer, Alan Kim Johnson and Stephen J Lewis

Vascular pharmacology, Vol.45(2), pp.102-111

08/2006

DOI: 10.1016/j.vph.2006.03.006

PMID: 16697265

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Abstract

This study examined the hypothesis that intracellular cGMP stimulates the release of catecholamines from sympathetic nerve terminals (SNTs) in conscious rats. Conscious rats were prepared to determine the effects of intravenously-administered agents on heart rate (HR) and mean arterial blood pressure (MAP). Bolus intravenous injections of the membrane-permeable cGMP analogue, 8-(4-chlorophenylthio)-cGMP (8-CPT-cGMP), elicited immediate and pronounced increases in HR before any changes in MAP were observed. In contrast, injections of cGMP did not elicit changes in HR or MAP. The 8-CPT-cGMP-induced tachycardia was markedly diminished by (1) the beta(1,2)-adrenoceptor antagonist, propranolol, (2) the ganglion blocking agent, chlorisondamine, and (3) bretylium, which blocks Ca2+-dependent mobilization of vesicular stores of catecholamines from SNTs. 8-CPT-cGMP also elicited minor falls in MAP in propranolol-treated rats but elicited pronounced falls in MAP in rats treated with chlorisondamine, bretylium, or combined administration of bretylium and the muscarinic receptor antagonist, methyl-atropine. These findings suggest that (1) intracellular cGMP elicits the release of Ca2+-sensitive and Ca2+-insensitive stores of catecholamines from SNTs in conscious rats, and (2) cGMP-mediated release of catecholamines from SNTs antagonizes cGMP-mediated relaxation of vascular smooth muscle in resistance arteries. Taken together, these findings support the concept that increases in intracellular cGMP levels by atrial natriuretic peptide and endothelium- and cardiac-derived nitric oxide regulate sympathetic control of the heart and the microvasculature of conscious rats via cGMP-dependent release of catecholamines.

Animals

Blood Pressure - drug effects

Calcium - metabolism

Calcium Signaling

Catecholamines - metabolism

Catecholamines - secretion

Consciousness

Cyclic GMP - analogs & derivatives

Cyclic GMP - pharmacology

Cyclic GMP - physiology

Heart Rate - drug effects

Intracellular Fluid - metabolism

Male

Presynaptic Terminals - metabolism

Presynaptic Terminals - secretion

Rats

Rats, Sprague-Dawley

Sympathetic Nervous System - drug effects

Sympathetic Nervous System - physiology

Thionucleotides - pharmacology

Details

Title: Subtitle: Intracellular cGMP may promote Ca2+-dependent and Ca2+-independent release of catecholamines from sympathetic nerve terminals
Creators: Erin J Whalen - Department of Psychology, University of Iowa, Iowa City, IA 52242, USA. ewhalen@receptor-biol.duke.edu
Timothy B Saurer
Alan Kim Johnson
Stephen J Lewis
Resource Type: Journal article
Publication Details: Vascular pharmacology, Vol.45(2), pp.102-111
DOI: 10.1016/j.vph.2006.03.006
PMID: 16697265
ISSN: 1537-1891
eISSN: 1879-3649
Grant note: HL 14388 / NHLBI NIH HHS HL57472 / NHLBI NIH HHS
Language: English
Date published: 08/2006
Academic Unit: Psychological and Brain Sciences; Neuroscience and Pharmacology; Health and Human Physiology
Record Identifier: 9984213406902771

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