Document Detail

Pretreatment with the nitric oxide donor SNAP or nerve transection blocks humoral preconditioning by remote limb ischemia or intra-arterial adenosine.
MedLine Citation:
PMID:  20802131     Owner:  NLM     Status:  MEDLINE    
We have previously shown that remote ischemic preconditioning (rIPC) by transient limb ischemia leads to the release of a circulating factor(s) that induces potent myocardial protection. Intra-arterial injection of adenosine into a limb also leads to cardioprotection, but the mechanism of its signal transduction is poorly understood. Eleven groups of rabbits received saline control or rIPC or adenosine administration with additional pretreatment with the nitric oxide (NO) synthase blocker N(G)-nitro-l-arginine methyl ester, the NO donor S-nitroso-N-acetylpenicillamine, its non-NO-donating derivative N-acetylpenicillamine, or femoral nerve section. Blood was then drawn from each animal, and the dialysate of the plasma was used to perfuse a naïve heart from an untreated donor. Infarct size was measured after 30 min of global ischemia and 120 min reperfusion. When compared with that of the control, mean infarct size was significantly smaller in groups treated with rIPC alone (P < 0.01) and intra-arterial adenosine (P < 0.01). Pretreatment with N(G)-nitro-l-arginine methyl ester or N-acetylpenicillamine did not affect the level of protection induced by rIPC (P = not significant, compared with rIPC alone) or intra-arterial adenosine (P = not significant, compared with intra-arterial adenosine alone), but prior femoral nerve transection or pretreatment with S-nitroso-N-acetylpenicillamine abolished the cardioprotective effect of intra-arterial adenosine and rIPC. Intra-arterial adenosine, like rIPC, releases a blood-borne cardioprotective factor(s) that is dependent on an intact femoral nerve and is inhibited by pretreatment with a NO donor. These results may be important when designing or assessing the results of clinical trials of adenosine or rIPC cardioprotection, where NO donors are used as part of therapy.
Tor Steensrud; Jing Li; Xiaojing Dai; Cedric Manlhiot; Rajesh K Kharbanda; Michael Tropak; Andrew Redington
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-27
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-11-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1598-603     Citation Subset:  IM    
Department of Cardio-Thoracic and Vascular Surgery, University Hospital North Norway, Tromsø, Norway.
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MeSH Terms
Adenosine / administration & dosage,  pharmacology*
Enzyme Inhibitors / pharmacology
Femoral Nerve / surgery*
Hindlimb / blood supply*,  innervation
Injections, Intra-Arterial
Ischemia / metabolism*
Ischemic Preconditioning*
Models, Animal
Myocardial Infarction / metabolism,  pathology
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism
Nitric Oxide Donors / pharmacology*
S-Nitroso-N-Acetylpenicillamine / pharmacology*
Signal Transduction / drug effects,  physiology
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 58-61-7/Adenosine; 79032-48-7/S-Nitroso-N-Acetylpenicillamine

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

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