Document Detail

Nitric oxide-cGMP pathway is involved in endotoxin-induced contractile dysfunction in rat hearts.
MedLine Citation:
PMID:  14555681     Owner:  NLM     Status:  MEDLINE    
The mechanisms by which endotoxemia causes cardiac depression have not been fully elucidated. The present study examined the involvement of nitric oxide (NO) in this pathology. Rats were infused with lipopolysaccharide (LPS) or saline, and the plasma and myocardial NO(2)(-) and NO(3)(-) (NOx) concentrations were measured before or 3, 6, and 24 h after treatment. The hearts were then immediately isolated and mounted in a Langendorff apparatus, and left ventricular developed pressure (LVDP) was determined before biochemical analysis of the myocardium. LPS injection effected the expression of inducible NO synthase (iNOS) in the myocardium, a marked increase in plasma and myocardial NOx levels, and a significant decline in LVDP compared with saline controls. The LPS-induced NO production and concomitant cardiac depression were most pronounced 6 h after LPS injection and were accompanied by a significant increase in myocardial cGMP content. Myocardial ATP levels were not significantly altered after LPS injection. Significant negative correlation was observed between LVDP and myocardial cGMP content, as well as between LVDP and plasma NOx levels. Aminoguanidine, an inhibitor of iNOS, significantly attenuated the LPS-induced NOx production and contractile dysfunction. Furthermore, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, significantly decreased myocardial cGMP content and attenuated the contractile depression, although aminoguanidine or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one was not able to completely reverse myocardial dysfunction. Our data suggest that endotoxin-induced contractile dysfunction in rat hearts is associated with NO production by myocardial iNOS and a concomitant increase in myocardial cGMP.
Tetsuya Tatsumi; Natsuya Keira; Kazuko Akashi; Miyuki Kobara; Satoaki Matoba; Jun Shiraishi; Satoshi Yamanaka; Akiko Mano; Mitsuo Takeda; Susumu Nishikawa; Jun Asayama; Henry Fliss; Masao Nakagawa
Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article     Date:  2003-10-10
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  96     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-09     Completed Date:  2004-10-05     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  853-60     Citation Subset:  IM    
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
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MeSH Terms
Cyclic GMP / physiology*
Endotoxins / toxicity*
Myocardial Contraction / drug effects,  physiology*
Myocardium / metabolism*
Nitric Oxide / antagonists & inhibitors,  physiology*
Rats, Sprague-Dawley
Signal Transduction / drug effects,  physiology*
Ventricular Dysfunction, Left / chemically induced,  metabolism*,  physiopathology
Reg. No./Substance:
0/Endotoxins; 10102-43-9/Nitric Oxide; 7665-99-8/Cyclic GMP

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