Intracellular cGMP may promote Ca2+-dependent and Ca2+-independent release of catecholamines from sympathetic nerve terminals.
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.
Whalen
Erin J
EJ
Department of Psychology, University of Iowa, Iowa City, IA 52242, USA. ewhalen@receptor-biol.duke.edu
Saurer
Timothy B
TB
Johnson
Alan Kim
AK
Lewis
Stephen J
SJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002395:Catecholamines / Q000378:metabolism*; D003243:Consciousness; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D002395:Catecholamines; D013873:Thionucleotides; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D006152:Cyclic GMP; D002118:Calcium