Cardiovascular and pulmonary effects of NOS inhibition in endotoxemic conscious rats subjected to swimming training

Life Sci. 2007 Sep 29;81(16):1301-8. doi: 10.1016/j.lfs.2007.09.006. Epub 2007 Sep 19.

Abstract

Sepsis is characterized by systemic hypotension, hyporeactiveness to vasoconstrictors, impaired tissue perfusion, and multiple organ failure. During exercise training (ET), dynamic cardiovascular adjustments take place to maintain proper blood pressure and adjust blood supply to different vascular beds. The aim of this study was to investigate whether ET protects against the cardiovascular abnormalities induced by LPS, a model of experimental endotoxemia, and to evaluate the role of nitric oxide (NO) in pulmonary edema. Wistar rats were subjected to swimming training (up to 1 h/day, 5 days/week for 4 weeks) after which their femoral artery and vein were catheterized. LPS (5 mg/kg, i.v.), injected in control (C) and trained animals (ET), promoted 3 distinct phases in mean arterial pressure (MAP) and heart rate (HR). After ET the alterations in MAP were attenuated. The ET animals showed a lower pulmonary edema index (PEI) after LPS (C=0.65+/-0.01; ET=0.60+/-0.02), which was attenuated after treatment with aminoguanidine in both groups (C=0.53+/-0.02; ET=0.53+/-0.02, p<0.05). After l-NAME, PEI was enhanced numerically in the C and was statistically higher in the ET group (C=0.73+/-0.05; ET=1.30+/-0.3, p<0.05). 7-nitroindazole did not promote any alteration in either group. The adaptations promoted by ET seem to be beneficial, counteracting the cardiovascular abnormalities and pulmonary edema seen in septicemia induced by LPS. The results suggest that iNOS aggravates and cNOS protects against this pulmonary edema.

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Body Weight / drug effects
  • Disease Models, Animal
  • Endotoxemia / complications
  • Endotoxemia / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Heart Rate / drug effects*
  • Lipopolysaccharides / toxicity
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / biosynthesis
  • Organ Size / drug effects
  • Pulmonary Edema* / enzymology
  • Pulmonary Edema* / etiology
  • Pulmonary Edema* / physiopathology
  • Rats
  • Rats, Wistar
  • Swimming
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide, E. coli O26-B6
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat