Document Detail

The preoptic anterior hypothalamic area mediates initiation of the hypotensive response induced by LPS in male rats.
MedLine Citation:
PMID:  18386391     Owner:  NLM     Status:  MEDLINE    
The mechanism responsible for the initiation of endotoxic hypotension is not fully understood, although it is often attributed to a direct effect of LPS and other vasoactive mediators on the vasculature. Alternatively, recent evidence raises the possibility that endotoxic hypotension may be initiated through a central mechanism. Previous studies have shown that LPS initiates fever, sickness behavior, and other aspects of the inflammatory response through a neural pathway that sends peripheral inflammatory signals to the preoptic anterior hypothalamic area (POA). It is also well known that the POA plays a role in the regulation of cardiovascular function, but its involvement in LPS-induced hypotension has not been examined previously. Therefore, the aim of the present paper was to investigate whether the initial abrupt fall in arterial pressure evoked by LPS in septic shock is mediated by the POA. LPS (1 mg/kg, i.v.) administration to halothane-anesthetized or conscious rats lowered arterial blood pressure by 24.8+/-2.9 and 25.1+/-5.8 mmHg, respectively. Bilateral lidocaine (2%; 1 microL) injection into the POA, but not the lateral hypothalamus, prevented the hypotension evoked by LPS entirely in both anesthetized and conscious animals. Remarkably, this blockade significantly inhibited the second, delayed fall in arterial pressure induced by LPS, and simultaneously decreased TNF-alpha plasma levels. Together, these data indicate that the initial phase of endotoxic hypotension is mediated by the POA and suggest that the initiation of the hypotensive response induced by LPS can be essential for the development of the late fall in blood pressure.
Mustafa S Yilmaz; William R Millington; Carlos Feleder
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  29     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-04-02     Completed Date:  2008-07-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  232-7     Citation Subset:  IM    
Department of Pharmaceutical Sciences, Albany College of Pharmacy, Albany, New York 12208, USA.
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MeSH Terms
Anterior Hypothalamic Nucleus / drug effects*,  physiopathology
Blood Pressure / drug effects*
Hypotension / chemically induced,  physiopathology*,  prevention & control
Lidocaine / pharmacology
Lipopolysaccharides / toxicity*
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha / blood
Reg. No./Substance:
0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 137-58-6/Lidocaine

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