NITRIC-OXIDE MODULATES SYMPATHETIC VASOCONSTRICTION AND BASAL BLOOD-FLOW IN NORMAL AND ACUTELY INFLAMED RABBIT KNEE JOINTS

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 es ter (L-NAME), a NO production inhibitor, reduced basal joint blood flo w, 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 kne e 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 respons es to electrical stimulation of the posterior articular nerve (PAN) we re significantly smaller in the inflamed joint compared to normal. Inf usion of L-NAME for 45 min resulted in an increased vasoconstrictor re sponse by 78% in normal and 79% in inflamed joints. Subsequent close i ntra-arterial infusion Of L-arginine failed to return the enhanced vas oconstrictor responses induced by L-NAME to their control levels in bo th normal and test animal groups, but partially restored blood flow ch anges. In both normal and inflamed joints, vasoconstriction produced b y separate intra-arterial injection of the alpha1-agonist phenylephrin e (2.5 nmol) or either of the alpha2-agonists clonidine (250 pmol) and UK-14304 (250 pmol) was increased significantly by L-NAME infusion bu t not completely restored to basal values by L-arginine infusion. The control responses to all three agents did not differ significantly bet ween normal and inflamed knees. The results of this study show that NO maintains the vessels of both normal and inflamed joints dilated and plays a major role in regulation of their basal tone and thus articula r blood flow. Also, NO plays an important role in modulation of sympat hetic nerve-mediated effects on joint blood flow. Within the confines of the present study, the rate of NO production does not appear to be changed by the process of acute inflammation.