Document Detail

Platelet activation and modulation of the induction of nitric oxide synthase in the conscious rat.
MedLine Citation:
PMID:  10530798     Owner:  NLM     Status:  MEDLINE    
Injection of lipopolysaccharide (LPS) (Salmonella W. Typhosa i.v. bolus) into conscious rats, induced a rapid drop of circulating platelets analogous to that induced by ADP. The animals showed a small fall in mean arterial blood pressure (MABP), an increase in heart rate and a significant increase in plasma nitrite and nitrate level. This result is consistent with the stimulation of an inducible NO synthase (i-NOS). The administration of the stable prostacyclin analogue, iloprost plus ADP or LPS, significantly protected against the decrease in free platelet number induced by ADP or LPS. The plasma nitrite and nitrate level stimulated by LPS was significantly reduced by iloprost and also by prostacyclin. These results are consistent with an inhibition of i-NOS by agents that increase the intracellular level of cAMP. The administration of the NO donor S-Nitroso-N-acyl-D-penicillamine (SNAP) plus ADP or LPS, significantly prevented thrombocytopenia induced by ADP and by LPS. SNAP did not decrease the plasma nitrite and nitrate level stimulated by LPS; furthermore it induced a significant increase of heart rate, without affecting MABP, suggesting a direct accelerating effect of NO on the sino-atrial node. The administration of S-nitroso-glutathione (GSNO), a stable nitrosothiol, plus ADP or LPS, significantly prevented thrombocytopenia induced by ADP but not by LPS. GSNO significantly reduced the plasma nitrite and nitrate level stimulated by LPS. These data demonstrate that the L-Arginine: NO pathway in vivo may be modulated by prostanoids and that compounds which increase cAMP, such as iloprost, are able to protect against LPS-induced early thrombocytopenia.
S Picunio; M Simioni; M G Doni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Life sciences     Volume:  65     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1999  
Date Detail:
Created Date:  1999-11-05     Completed Date:  1999-11-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1463-75     Citation Subset:  IM    
Institute of Human Physiology, Faculty of Medicine and Surgery, University of Padova, Italy.
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MeSH Terms
Adenosine Diphosphate / pharmacology
Blood Pressure / drug effects
Enzyme Induction
Heart Rate / drug effects
Iloprost / pharmacology
Lipopolysaccharides / pharmacology
Nitrates / blood
Nitric Oxide Synthase / biosynthesis*
Nitric Oxide Synthase Type II
Nitrites / blood
Penicillamine / analogs & derivatives,  pharmacology
Platelet Activation*
Platelet Count / drug effects
Rats, Wistar
Thrombocytopenia / blood*,  chemically induced
Reg. No./Substance:
0/Lipopolysaccharides; 0/Nitrates; 0/Nitrites; 0/S-nitro-N-acetylpenicillamine; 52-67-5/Penicillamine; 58-64-0/Adenosine Diphosphate; 78919-13-8/Iloprost; EC Oxide Synthase; EC Oxide Synthase Type II; EC protein, rat

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