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

OBJECTIVETo study the expression (mRNA and protein) and activity of the constitutive isoforms of nitric oxide synthase (NOS1 and NOS3) in a skeletal muscle of septic patients. DESIGNProspective study. SETTINGAn adult trauma/surgical intensive care unit in an urban teaching hospital. PATIENTSSixteen septic patients and 21 controls. INTERVENTIONSNone. MEASUREMENTS AND MAIN RESULTS Samples of the rectus abdominis muscle were obtained during surgical procedure. NOS mRNA, protein, and activity were detected by reverse-transcriptase polymerase chain reaction, Western blot, and the conversion of []l-arginine to []l-citrulline, respectively. The main results of this study are as followsa) Levels of NOS1 mRNA and protein 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 associated with a reduction in constitutive NOS activity; and d) modifications of NOS1 and NOS3 protein expression were correlated significantly with the severity of sepsis, assessed by the Simplified Acute Physiology Score II. CONCLUSIONSSepsis induces reciprocal expressional modifications of NOS1 and NOS3 in human skeletal muscle, which decreases muscular constitutive NOS activity. These modifications may have implications for muscle impairment in septic patients.