Experiments were performed to investigate the role of nitric oxide (NO) in the regulation of joint blood flow and in modulating sympathetic vasoconstrictor influences in normal and acutely inflamed rabbit knees. Close intra-arterial infusion of N omega-nitro_L-arginine methyl ester (L-NAME), a NO production inhibitor, reduced basal joint blood flow, measured by laser Doppler flowmetry, by 36.4 +/- 5.1% (mean +/- S.E.M.) in normal (control) and 21.4 +/- 7.8% in carrageenan-inflamed knee joints. Mean systemic arterial blood pressure was increased by 20 +/- 3.1 and 17.9 +/- 2% in control and test animal groups respectively. Joint vascular resistance was increased by 101 +/- 19% in normal and 68.9 +/- 13.7% in carrageenan-treated animals. Vasoconstrictor responses to electrical stimulation of the posterior articular nerve (PAN) were significantly smaller in the inflamed joint compared to normal. Infusion of L-NAME for 45 min resulted in an increased vasoconstrictor response by 78% in normal and 79% in inflamed joints. Subsequent close intra-arterial infusion of L-arginine failed to return the enhanced vasoconstrictor responses induced by L-NAME to their control levels in both normal and test animal groups, but partially restored blood flow changes. In both normal and inflamed joints, vasoconstriction produced by separate intra-arterial injection of the alpha 1-agonist phenylephrine (2.5 nmol) or either of the alpha 2-agonists clonidine (250 pmol) and UK-14304 (250 pmol) was increased significantly by L-NAME infusion but not completely restored to basal values by L-arginine infusion. The control responses to all three agents did not differ significantly between normal and inflamed knees.(ABSTRACT TRUNCATED AT 250 WORDS)

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