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Vascul Pharmacol. 2006 Aug;45(2):102-11. Epub 2006 May 11.

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

Author information

1
Department of Psychology, University of Iowa, Iowa City, IA 52242, USA. ewhalen@receptor-biol.duke.edu

Abstract

OBJECTIVE:

This study examined the hypothesis that intracellular cGMP stimulates the release of catecholamines from sympathetic nerve terminals (SNTs) in conscious rats.

METHODS:

Conscious rats were prepared to determine the effects of intravenously-administered agents on heart rate (HR) and mean arterial blood pressure (MAP).

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
16697265
DOI:
10.1016/j.vph.2006.03.006
[Indexed for MEDLINE]

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