title: The preoptic anterior hypothalamic area mediates initiation of the hypotensive response induced by LPS in male rats.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Albany College of Pharmacy, Albany, New York 12208, USA.
authors.forename: Mustafa S
authors.initials: MS
authors.lastname: Yilmaz
authors.forename: William R
authors.initials: WR
authors.lastname: Millington
authors.forename: Carlos
authors.initials: C
authors.lastname: Feleder
mesh_terms: D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D008012:Lidocaine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008012:Lidocaine