title: Effect of sodium arsenite on iNOS expression and vascular hyporeactivity associated with cecal ligation and puncture in the rat.
abstract: Induction of the heat shock response protects animals from either endotoxemia or peritonitis. In endotoxemia, heat shock protein (HSP) induction is associated with reversal of vascular hyporeactivity and inhibition of iNOS expression. Recent studies suggest differences in the inflammatory mechanisms during endotoxemia and peritonitis animal models and their response to therapeutic interventions. We therefore studied the effect of the HSP inducer sodium arsenite (SA) on vascular reactivity and iNOS expression in rats undergoing cecal ligation and puncture (CLP). CLP resulted in suppression of the pressor effect of norepinephrine (NE) in vivo (measured by changes in blood pressure in response to NE boluses) and ex vivo (changes in contraction force in isolated mesenteric arteries in response to NE concentrations), and in the expression of iNOS protein. Pretreatment of the rats with SA resulted in reversal of CLP-induced vascular hyporeactivity in vivo and ex vivo, and inhibition of iNOS expression after 22 h. SA pretreatment improved 7-day survival after CLP from 18.2% to 70% (P < 0.005). Glucocorticoid receptor inhibition did not affect the effect of HSP induction on iNOS expression. The similarity of the effect of HSP on vascular reactivity and iNOS expression in two distinct sepsis models suggests that this effect may be clinically important and that a causative relationship between HSP induction, iNOS inhibition, and reversal of vascular reactivity is likely.
authors.affiliation: Division of Pediatric Critical Care Medicine, Georgetown University Children's Medical Center, Washington, District of Columbia 20007, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Hauser
authors.forename: K
authors.initials: K
authors.lastname: Wasserloos
authors.forename: E K
authors.initials: EK
authors.lastname: Dayao
authors.forename: B R
authors.initials: BR
authors.lastname: Pitt
mesh_terms: D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D002432:Cecum / Q000601:surgery; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D008026:Ligation; D008297:Male; D008643:Mesentery; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D017670:Sodium Compounds / Q000494:pharmacology*; D015996:Survival Rate; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D018053:Arsenites; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; D014662:Vasoconstrictor Agents; C017947:sodium arsenite; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D009638:Norepinephrine