Document Detail

Endocardial endothelium mediates luminal ACh-NO signaling in isolated frog heart.
MedLine Citation:
PMID:  9950865     Owner:  NLM     Status:  MEDLINE    
ACh exerted a biphasic effect in the in vitro working heart of Rana esculenta. High concentrations (10(-7) M) of ACh depressed stroke volume (SV) and stroke work (SW) by approximately 30% with a shorter systolic phase and reduced peak pressure. Doses from 10(-10) M induced a positive response peaking at 10(-8) M (SV: +8.6%; SW: +6. 5%) and a prolonged systolic phase without affecting peak pressure. Atropine and pirenzepine blocked both the positive and the negative effects of ACh. Pretreatment with Triton X-100 (0.1 ml, 0.05%) or with nitric oxide (NO)-cGMP pathway antagonists (NG-nitro-L-arginine, NG-nitro-L-arginine methyl ester, NG-monomethyl-L-arginine, and 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one) abolished the positive and negative cholinergic effects. Infusion of 8-bromoguanosine 3', 5'-cyclic monophosphate reverted the positive effect of ACh to a negative effect. Milrinone blocked the positive inotropism but did not change the negative cholinergic response. The NO donor 3-morpholinosydnonimine generated a biphasic dose-response curve with a maximum positive effect at 10(-8) M (SV: +8%; SW: +5.6%; systolic phase: +28 ms) and a negative effect at 5 x 10(-8) M (SV and SW: about -12%; systolic phase: -70 ms; peak pressure: -1.50 mm). We conclude that in the avascular frog heart the endocardial endothelium mediates the inotropic effect of luminal cholinergic stimuli via a NO-cGMP pathway.
A Gattuso; R Mazza; D Pellegrino; B Tota
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  276     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-30     Completed Date:  1999-03-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H633-41     Citation Subset:  IM    
Dipartimento di Biologia Cellulare, Università della Calabria, 87030 Arcavacata di Rende, Italy.
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MeSH Terms
Acetylcholine / pharmacology*
Endocardium / physiology*,  physiopathology
Endothelium / physiology,  physiopathology
Heart / drug effects,  physiology*
Myocardial Contraction / drug effects
Nitric Oxide / physiology*
Rana esculenta
Signal Transduction / physiology*
Ventricular Dysfunction / physiopathology
Reg. No./Substance:
10102-43-9/Nitric Oxide; 51-84-3/Acetylcholine

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