title: Atrial natriuretic peptide alleviates cardiovascular and metabolic disorders in a rat endotoxemia model: a possible role for its anti-inflammatory properties.
abstract: BACKGROUND
  Atrial natriuretic peptide (ANP) plays important roles in the regulation of cardiovascular and renal homeostasis. Furthermore, several studies have shown that ANP may have anti-inflammatory activities. We hypothesized that ANP may alleviate cardiovascular and/or metabolic disorders in rats with lipopolysaccharide (LPS)-induced endotoxemia.
  
  
  METHODS
  In rats anesthetized with pentobarbital, LPS was injected and ANP was continuously infused at 0.15 µg/kg/min. Mean arterial pressure and pulse rate were monitored hourly, and arterial blood gases were analyzed before LPS injection and at 1, 4, and 6 hours after LPS injection. The expression in the rat left ventricle of mRNAs encoding nitric oxide synthase 2 and 3 (iNOS, eNOS), heme oxygenase 1 and 2 (HO-1, 2), tumor necrosis factor α (TNFα), and interleukin (IL)-1β was measured with the real-time reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  LPS increased the expression of TNFα, IL-1β, iNOS, and HO-1, which was inhibited by infusion of ANP. Furthermore, the LPS-induced decrease in mean arterial pressure was attenuated, and the acid-base imbalance caused by increased lactate production was improved 6 hours after the administration of ANP.
  
  
  CONCLUSIONS
  Our results suggest that continuous infusion of ANP counteracts the cardiovascular and metabolic disorders associated with endotoxemia, possibly via anti-inflammatory mechanisms.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. nobunaga3@nms.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamanashi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sakamoto
mesh_terms: D000138:Acidosis / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D019446:Endotoxemia / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D009320:Atrial Natriuretic Factor