EFFECT OF NITRIC-OXIDE SYNTHASE INHIBITOR ON DIAPHRAGMATIC FUNCTION AFTER RESISTIVE LOADING

We studied the effect of a nitric oxide synthase inhibitor, N-omega-Ni tro-L-arginine-methyl-ester (L-NAME), on in vitro diaphragmatic functi on both at rest (control) or after inspiratory resistive loading (IRL) . Sprague-Dawley rats were anesthetized, instrumented, and then the fo llowing experimental groups: (1) controls; (2) L-NAME (100 mg/kg/body weight intravenously alone); (3) IRL alone; and (4) L-NAME + IRL. The IRL protocol consisted of applying a variable resistor to the inspirat ory limb of a two-way valve at 70% of maximal airway pressure until ap nea. After the experiment, the animals were sacrificed and diaphragmat ic strips were obtained for activity of constitutive nitric oxide synt hase (cNOS) and measurements of in vitro contractile properties: tetan ic (Po) and twitch tensions (Pt). cNOS activity was significantly decr eased in the L-NAME and L- NAME + IRL groups (P less than or equal to 0.05) as compared with control and IRL groups. L-NAME alone did not af fect Po or Pt. However, in both IRL groups, with and without was a sig nificant decrease in Po and Pt. This reduction was comparable in both groups. In summary, our data showed that L-NAME resulted in a signific ant decrease cNOS activity, bur. in vitro contractility was impaired, COMP BIOCHEM PHYSIOL 119A;1:185-190, 1998. (C) 1998 Elsevier Science I nc.