Document Detail

The role of nitric oxide, K(+)(ATP) channels, and cGMP in the preconditioning response of the rabbit.
MedLine Citation:
PMID:  10864483     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The role of nitric oxide (NO), K(+)(ATP) channels, and cyclic GMP (cGMP) in preconditioning is unknown. MATERIAL AND METHODS: Isolated rabbit hearts were pretreated with the NO precursor L-arginine (L-Arg), both alone and after infusion of the NO synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Guanylate cyclase inhibitor methylene blue (MB) was infused prior to L-Arg in a separate group of hearts. To contrast the mechanisms of NO preconditioning and potassium channel opener (PCO) preconditioning, we infused the PCO pinacidil after L-NAME and the PCO blocker glibenclamide before L-Arg. Control hearts had no drug infused. The LAD coronary artery was occluded for 1 h and reperfused for 1 h in all hearts. Action potential duration (APD(50)), coronary flow (CF), and left ventricular developed pressure (DP) were measured, and infarct size (IS) was determined and expressed as a percentage of the area at risk. RESULTS: L-Arg prolonged APD(50) at 60 min of reperfusion (94 +/- 6 ms vs 69 +/- 2 ms (control) vs 70 +/- 2 ms (L-NAME) vs 74 +/- 3 ms (MB), P < 0.05). L-Arg reduced IS compared with control (24 +/- 2% vs 49 +/- 3%, P < 0.05); this was reversed by either L-NAME (53 +/- 4%, P < 0.05) or MB (43 +/- 3%, P < 0.05), but not by glibenclamide (20 +/- 4%), unlike the increase in CF during L-Arg infusion, which was blocked by glibenclamide. Pinacidil infusion decreased IS (26 +/- 2%), but this effect was blocked by L-NAME (53 +/- 7%, P < 0.05 vs pinacidil), although L-NAME did not blunt the increase in CF. There were no significant differences in DP among groups. CONCLUSION: L-Arginine preconditions the heart through NO generation, and this response is mediated through a cGMP-dependent mechanism, but is independent of the K(+)(ATP) channels. Coronary vasodilation is mediated through a mechanism different from that responsible for cardiomyocyte preconditioning.
H Horimoto; G R Gaudette; A E Saltman; I B Krukenkamp
Related Documents :
11566903 - Splenorenal reflex regulation of arterial pressure.
10588943 - Vascular effects of arachidonic acid in the rat perfused heart. role of the endothelium...
11541703 - Measurement of the partial oxygen pressure and oxygen utilization in the skin of cosmon...
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  The Journal of surgical research     Volume:  92     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-07-24     Completed Date:  2000-07-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  56-63     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Division of Cardiothoracic Surgery and The Institute for Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Action Potentials / physiology
Adenosine Triphosphate / metabolism
Arginine / pharmacology
Coronary Circulation / drug effects
Cyclic GMP / metabolism*
Enzyme Inhibitors / pharmacology
Ischemic Preconditioning*
Methylene Blue / pharmacology
Muscle Fibers, Skeletal / physiology
Myocardial Infarction / metabolism
Myocardial Ischemia / metabolism*
Myocardium / chemistry,  cytology,  metabolism
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism*
Potassium Channels / metabolism*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Potassium Channels; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 56-65-5/Adenosine Triphosphate; 61-73-4/Methylene Blue; 74-79-3/Arginine; 7665-99-8/Cyclic GMP

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Peer teaching and computer-assisted learning: An effective combination for surgical skill training?
Next Document:  Late-gestation tracheal occlusion in the fetal lamb causes rapid lung growth with type II cell prese...