title: Nitric oxide synthase inhibition during experimental sepsis improves renal excretory function in the presence of chronically increased atrial natriuretic peptide.
abstract: OBJECTIVE
  To test whether renal excretory function decreases after nitric oxide synthase inhibition during experimental hyperdynamic sepsis.
  
  
  METHODS
  Prospective, randomized, controlled animal trial.
  
  
  METHODS
  Research laboratory at a large university medical center.
  
  
  METHODS
  Chronically instrumented Merino breed ewes (n = 18).
  
  
  METHODS
  Continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) for the experimental period of 32 hrs. One group received a bolus of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (25 mg/kg), after 24 hrs, and the remaining sheep were given the carrier, sodium chloride 0.9%.
  
  
  RESULTS
  The sheep developed a hyperdynamic cardiovascular response characterized by a decrease in systemic vascular resistance index (p < .05), and an increased cardiac index (p < .05) by 24 hrs. The sheep retained fluid, with creatinine clearance decreasing in the presence of chronically increased atrial natriuretic peptide. After the administration of N omega-nitro-L-arginine methyl ester, systemic vascular resistance index and cardiac index returned to baseline values, fluid balance normalized, and glomerular filtration rate increased (p < .05), while the control animals continued to retain fluid and their creatinine clearance continued to decrease. The concentrations of atrial natriuretic peptide did not differ significantly between groups after N omega-nitro-L-arginine methyl ester administration.
  
  
  CONCLUSIONS
  In this ovine model of experimental hyperdynamic sepsis, renal excretory function decreases in the presence of chronically increased concentrations of atrial natriuretic peptide. Administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, reverses the vasodilatory state, thereby improving fluid balance and glomerular filtration.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0833, USA.
authors.forename: F
authors.initials: F
authors.lastname: Hinder
authors.forename: M
authors.initials: M
authors.lastname: Booke
authors.forename: L D
authors.initials: LD
authors.lastname: Traber
authors.forename: N
authors.initials: N
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: S
authors.initials: S
authors.lastname: Rogers
authors.forename: D L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004731:Endotoxins; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018805:Sepsis / Q000097:blood / Q000503:physiopathology*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D004731:Endotoxins; D009320:Atrial Natriuretic Factor; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester