Sepsis is associated with reciprocal expressional modifications of constitutive nitric oxide synthase (NOS) in human skeletal muscle: Down-regulationof NOS1 and up-regulation of NOS3

Objective: To study the expression (mRNA and protein) and activity of the c onstitutive isoforms of nitric oxide synthase (NOS1 and NOS3) in a skeletal muscle of septic patients. Design: Prospective study. Setting: An adult trauma/surgical intensive care unit in an urban teaching hospital. Patients: Sixteen septic patients and 21 controls. Interventions: None. Measurements and Main Results: Samples of the rectus abdominis muscle were obtained during surgical procedure. NOS mRNA, protein, and activity were de tected by reverse-transcriptase polymerase chain reaction, Western blot, an d the conversion of [(3H)]L-arginine to [(3H)]L-citrulline, respectively. T he main results of this study are as follows: a) Levels of NOS1 mRNA and pr otein were significantly higher than those of NOS3 in the rectus abdominis muscle of control patients; b) NOS1 expression was down-regulated in septic patients, whereas NOS3 was up-regulated; c) these modulations were associa ted with a reduction in constitutive NOS activity; and d) modifications of NOS1 and NOS3 protein expression were correlated significantly with the sev erity of sepsis, assessed by the Simplified Acute Physiology Score II. Conclusions: Sepsis induces reciprocal expressional modifications of NOS1 a nd NOS3 in human skeletal muscle, which decreases muscular constitutive NOS activity. These modifications may have implications for muscle impairment in septic patients.