Lipopolysaccharide-induced hypotension is mediated by a neural pathway involving the vagus nerve, the nucleus tractus solitarius and alpha-adrenergic receptors in the preoptic anterior hypothalamic area.
We recently reported that the preoptic anterior hypothalamic area (POA) mediates the hypotensive response evoked by lipopolysaccharide (LPS). In this study, we investigated how the inflammatory signal induced by LPS reaches the POA. Subdiaphragmatic vagotomy and abdominal perivagal lidocaine administration, or lidocaine injection into the nucleus tractus solitarius (NTS) prevented LPS hypotension. Microinjection of the alpha-adrenergic receptor antagonist phentolamine into the POA, blocked initiation of the hypotensive response and prevented the late decompensatory phase. These data suggest that LPS hypotension is mediated by the vagus nerve which conveys the signal to the NTS and, in turn, stimulates norepinephrine release within the POA.
Yilmaz
M Sertac
MS
Department of Pharmaceutical Sciences, Albany College of Pharmacy, and Stratton VA Medical Center, Albany, NY 12208, USA.
Goktalay
Gokhan
G
Millington
William R
WR
Myer
Brian S
BS
Cutrera
Rodolfo A
RA
Feleder
Carlos
C
D000208:Acute Disease; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D007022:Hypotension / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology*; D008012:Lidocaine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D015398:Signal Transduction / Q000276:immunology; D017552:Solitary Nucleus / Q000503:physiopathology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*
D000317:Adrenergic alpha-Antagonists; D000779:Anesthetics, Local; D008070:Lipopolysaccharides; D011942:Receptors, Adrenergic, alpha; D008012:Lidocaine; D010646:Phentolamine