title: The OVLT initiates the fall in arterial pressure evoked by high dose lipopolysaccharide: evidence that dichotomous, dose-related mechanisms mediate endotoxic hypotension.
abstract: This study tested the hypothesis that lipopolysaccharide (LPS) lowers arterial pressure through two different mechanisms depending on the dose. Previously, we found that a low hypotensive dose of LPS (1mg/kg) lowers arterial pressure by activating vagus nerve afferents. Here we report that hypotension evoked by high dose LPS (15mg/kg) can be prevented by injecting lidocaine into the OVLT but not by vagotomy or inactivation of the NTS. The hypotension produced by both LPS doses was correlated with elevated extracellular norepinephrine concentrations in the POA and prevented by blocking alpha-adrenergic receptors. Thus, initiation of endotoxic hypotension is dose-related, mechanistically.
authors.affiliation: Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, United States.
authors.forename: Carlos
authors.initials: C
authors.lastname: Feleder
authors.affiliation: Department of Medical Pharmacology, Uludag University, Faculty of Medicine, Bursa 16059, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Sertac Yilmaz
authors.affiliation: Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, United States.
authors.forename: Jianya
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Medical Pharmacology, Uludag University, Faculty of Medicine, Bursa 16059, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Göktalay
authors.affiliation: Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, United States. Electronic address: william.millington@acphs.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Millington
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000633:toxicity*; D008297:Male; D066278:Organum Vasculosum / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides
keywords: Endotoxin; Lipopolysaccharide; OVLT; Preoptic area; Septic shock