Inhibition of nitric oxide production during electrical stimulation of the nerves supplying the rat knee joint.
A rôle for nitric oxide in the regulation of knee joint blood flow in the male anaesthetised rat was investigated using laser Doppler perfusion imaging. Intravenous infusion of the nitric oxide synthase inhibitor 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 resistance by about 15%. Mean arterial blood pressure was by and large unaffected by both dose of inhibitor during these first 5 min of infusion. The effect of an alternative nitric oxide synthase inhibitor NG-monomethyl-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 gradually rose throughout administration. Electrical stimulation of the saphenous nerve in control animals elicited a frequency-dependent constriction of articular blood vessels over the range 5-30 Hz. Nerve stimulation at lower frequencies had little effect on joint capsular perfusion. When the nerve was stimulated over the same range of frequencies but in the presence of L-NAME it was found that the frequency response profile was unaffected. However, intravenous infusion of the less potent inhibitor L-NMMA caused a greater vasoconstrictor response to nerve stimulation over all but the lowest frequency tested. The results of these experiments indicate that endogenous nitric oxide may be produced in only very small amounts by the vascular bed of the rat knee joint. 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 occur in the terminals of the nerves supplying the joint whose enzymatic activity is only inhibited by L-NMMA and not L-NAME.
McDougall
J J
JJ
Institute of Biological and Life Sciences, University of Glasgow, UK.
Ferrell
W R
WR
D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D004558:Electric Stimulation; D007719:Knee Joint / Q000378:metabolism*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009569:Nitric Oxide