Interstitial nitric oxide levels do not increase following L‐Arginine or ATP perfusion into the interstitium of rat hind‐limb skeletal muscle

Abstract

It has been proposed that increased extracellular L‐Arginine (L‐Arg) or ATP stimulates nitric oxide synthase activity producing nitric oxide (NO). In the present study we used the microdialysis technique to alter the interstitial concentration of L‐Arg and ATP to examine whether elevations in these compounds results in nitric oxide formation in rat skeletal muscle. Male Sprague‐Dawley rats were anaesthetized and had microdialysis fibers (1 cm diffusion length) inserted into the gastrocnemius muscle of each leg. Following 20 min. of baseline collection (saline), the microdialysis probes were perfused at a rate of 5 uL/min with either 20 mM L‐Arg (20 min., n = 10) or 60 uM ATP (20 min., n = 15). Interstitial NO concentrations were 7.2±1.1 and 5.2±0.7 uM during saline perfusion and did not change (P>0.05) following L‐Arg (6.5± 0.8 uM) or ATP (5.6±0.9 uM) perfusion. These data clearly demonstrate that elevated interstitial L‐Arg as well as ATP concentrations did not alter the basal interstitial concentrations of NO. Furthermore, these data suggest that the independent manipulation of L‐Arg and ATP in the interstitial space alone does not promote NO production and release from surrounding tissues.Supported by NSERC.