title: Role of nitric oxide in the hemodynamic changes of sepsis.
abstract: OBJECTIVE
  To study the role of nitric oxide in the hemodynamic changes of sepsis.
  
  
  METHODS
  Prospective, randomized, controlled, intervention study.
  
  
  METHODS
  Twenty-five sheep randomized to four groups: Group A (n = 8, nonseptic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) followed 15 mins later by L-arginine (200 mg/kg i.v.); group B (n = 4, nonseptic sheep) received L-arginine followed 15 mins later by NG-nitro L-arginine; group C (n = 7, septic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) alone; group D (n = 6, septic sheep) received L-arginine (200 mg/kg i.v.) followed by NG-nitro L-arginine (20 mg/kg i.v.).
  
  
  METHODS
  Sheep were anesthetized with pentobarbital, mechanically ventilated and monitored with a pulmonary artery catheter, a peripheral artery catheter, and a Miller catheter in the left ventricle. Sepsis was induced by the intravenous administration of live Escherichia coli (1.5 x 10(9) microorganisms/kg over 30 mins), which resulted in systemic hypotension, pulmonary hypertension, high cardiac output, and hyperlactatemia. Acetylcholine was administered before and after each intervention.
  
  
  RESULTS
  In nonseptic sheep (groups A and B) NG-nitro L-arginine induced an increase in mean blood pressure (BP), pulmonary arterial pressure, and systemic and pulmonary vascular resistances, accompanied by a decrease in cardiac index and the first derivative of left ventricular pressure. L-arginine administered to normal sheep induced systemic vasodilation. In the sepsis groups (groups C and D), the increases in BP and systemic vascular resistances induced by NG-nitro L-arginine were significant but less marked than in nonseptic sheep. Pretreatment of septic sheep with L-arginine totally abolished the NG-nitro L-arginine induced increases in systemic and pulmonary vascular resistances in this group. The administration of L-arginine in these animals induced both systemic and pulmonary vasodilation. Acetylcholine-mediated vasodilation was severely impaired in sepsis. In this condition, pretreatment with L-arginine improved the response to acetylcholine.
  
  
  CONCLUSIONS
  These data support the view that nitric oxide plays a significant role in modulating systemic and pulmonary vasomotor tone in normal and septic sheep. L-arginine produced systemic vasodilation in normal sheep, whereas both systemic and pulmonary vasodilation were observed in septic animals. The impaired response to an endothelium-dependent vasodilator in sepsis was improved by the previous administration of L-arginine.
authors: Hospital Universitario de Getafe, Madrid, Spain.
authors: J A
authors: JA
authors: Lorente
authors: L
authors: L
authors: Landín
authors: E
authors: E
authors: Renes
authors: R
authors: R
authors: De Pablo
authors: P
authors: P
authors: Jorge
authors: E
authors: E
authors: Ródena
authors: D
authors: D
authors: Liste
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D011897:Random Allocation; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine