Attenuation of vasoconstrictor response of knee joint blood vessels to (αl- adrenoceptor activation during chronic monoarthritis in rat: The role of nitric oxide

The effect of chronic inflammation induced by complete Freund's adjuvant (CFA) on anterior blood vessels of knee joint and its diameter was studied. Blood flow changes in response to phenylephrine (αl-adrenoceptor agonist) in CFA-treated and contralateral knee joints were observed over a 40-day period, using laser Doppler flowmetery (LDF) technique. Unilateral injection of CFA (0.2 ml) increased the diameter of injected knee at all days post-injection (p<0.001) and reached to its maximum level (49.7 ± 2%) at day 3. Then, the diameter decreased gradually but did not return to its initial value. In control animals, topical application of phenylephrine (10-13-10-17 M) to the exposed joint capsule decreased blood flow in a dose-dependent manner (11.1 ± 4.4 to 58.2 ± 4.5%, p<0.001). Unilateral injection of CFA attenuated the phenylephrine response in both ipsilateral and contralateral knees compared to the response of control animals (5.2 ± 1.6 to 48.3 ± 6.1% and 1.9 ± 2.2 to 45.3 ± 5.6 % respectively, p<0.05). The reduction persisted for three weeks after CFA injection (ipsilateral for 21 days contralateral for 30 days, p<0.001). Then, the above response returned to its normal value. To evaluate the role of nitric oxide (NO) on the observed responses, amino guanidine (inducible-NO synthase inhibitor) was injected (120 mg/kg/day, i.p.) in other groups of CFA-treated animals. Arninoguanidine potentiated (p<0.001) the vasoconstrictor response to phenylephrine in both CFA injected and contralateral knees at 7, 14 and 21 days post-injection, and the increment of knee joint diameter was also less prominent. These findings may indicate that the vasoconstrictor response to phenylephrine is decreased in chronic inflammation, and increased production of NO during chronic inflammation might be involved.