INHIBITION OF NITRIC-OXIDE PRODUCTION DURING ELECTRICAL-STIMULATION OF THE NERVES SUPPLYING THE RAT KNEE-JOINT

A role for nitric oxide in the regulation of knee joint blood flow in the male anaesthetised rat was investigated using laser Doppler perfus ion imaging. Intravenous infusion of the nitric oxide synthase inhibit or N-omega-nitro-L-arginine methyl ester (L-NAME) at a rate of 0.1 and 1 mg/kg per h caused an initial, but transient, rise in vascular resi stance by about 15%. Mean arterial blood pressure was by and large una ffected by both dose of inhibitor during these first 5 min of infusion . The effect of an alternative nitric oxide synthase inhibitor N-G-mon omethyl-L-arginine (L-NMMA) was also investigated. When 10 mg/kg per h of this drug was infused intravenously, there was a negligible effect on joint vascular resistance for the first 40 min but it then fell by about 15% over the next 20 min of infusion; mean arterial pressure gr adually rose throughout administration. Electrical stimulation of the saphenous nerve in control animals elicited a frequency-dependent cons triction of articular blood vessels over the range 5-30 Hz. Nerve stim ulation at lower frequencies had little effect on joint capsular perfu sion. When the nerve was stimulated over the same range of frequencies but in the presence of L-NAME it was found that the frequency respons e profile was unaffected. However, intravenous infusion of the less po tent inhibitor L-NMMA caused a greater vasoconstrictor response to ner ve stimulation over all but the lowest frequency tested. The results o f these experiments indicate that endogenous nitric oxide may be produ ced in only very small amounts by the vascular bed of the rat knee joi nt. This differs markedly from the findings of a previous study in the rabbit knee joint where L-NAME administration resulted in a large and sustained increase in vascular resistance, suggesting substantial and continuous NO release. A unique isoform of the enzyme may possibly oc cur in the terminals of the nerves supplying the joint whose enzymatic activity is only inhibited by L-NMMA and not L-NAME.