NITRIC-OXIDE MODULATES EXCITATION-CONTRACTION COUPLING IN THE DIAPHRAGM

We investigated the enzymatic source, cellular production, and functio nal importance of nitric oxide (NO) in rat diaphragm. Neuronal and end othelial isoforms of constituitive nitric oxide synthase (nc-NOS, ec-N OS) were identified by immunostaining. NOS activity measured in diaphr agm homogenates averaged 5.1 pmol/min/mg. Passive diaphragm fiber bund les produced NO derivatives (NOx) at the rate of 0.9 pmol/min/mg as me asured by the cytochrome c reduction assay; NO production was confirme d by photolysis/ chemiluminescence measurements. Endogenous NO depress ed diaphragm contractile function. The force of submaximal contraction was increased by NOS inhibitors, an effect that was stable for up to 60 min and was reversed by NO donors. We conclude that diaphragm muscl e fibers express nc-NOS, ec-NOS, or both; passive myocytes produce NOx ; and NO or NO-derivatives inhibit force production by modulating exci tation-contraction coupling. COMP BIOCHEM PHYSIOL 119A;1:211-218, 1998 . (C) 1998 Elsevier Science Inc.