Pathophysiological basis of acute inflammatory hyperaemia in the rat knee: roles of cyclo-oxygenase-1 and-2

Egan, C.G., Lockhart, J.C., Ferrell, W.R., Day, S.M. and McLean, J.S. (2002) Pathophysiological basis of acute inflammatory hyperaemia in the rat knee: roles of cyclo-oxygenase-1 and-2. Journal of Physiology, 539, pp. 579-587. (doi: 10.1113/jphysiol.2001.013473)

Full text not currently available from Enlighten.

Publisher's URL:


<p>The role of different isoforms of cyclo-oxygenase (COX) in mediating the acute (0-6 h) and late (24 h) phases of inflammation was investigated in the rat knee joint following intra-articular injection of carrageenan. The hyperaemic response was assessed transcutaneously using laser Doppler imaging (LDI). Samples were taken at corresponding time points for detection of synovial COX-1, COX-2 and inducible nitric oxide synthase (iNOS) mRNA, and measurement of urinary prostaglandin (PG) and nitric oxide metabolites (NO<sub>x</sub>). A non-selective COX inhibitor (indomethacin, 15 mg kg<sup>−1</sup>i.p.), a selective COX-2 inhibitor (SC-236, 16.8 mg kg<sup>−1</sup>i.p.) or vehicle were administered 1 h prior to carrageenan in the acute phase study. LDI scans were taken hourly for 4 h post-induction. Inflammatory hyperaemia in the vehicle group was attenuated in the indomethacin- (P < 0.001, two-way ANOVA) and SC-236-treated groups (P < 0.0001), with no difference between these treatments. At 24 h, i.v. infusion of indomethacin (0.1 mg min<sup>−1</sup>), increased vascular resistance (24 ± 7.1 %; P < 0.05) compared to vehicle infusion, whereas SC-236 (0.11 mg min<sup>−1</sup>) did not. Resistance changes to indomethacin also differed from SC-236 (P < 0.05). Knee joint diameter progressively increased over 24 h (P < 0.0001, one-way ANOVA). Urinary PG levels increased by 6 h (P < 0.05), but returned to baseline by 24 h. COX-1 mRNA was detectable at all time points; COX-2 mRNA only at 3 h. Urinary NOx levels increased progressively over 24 h (P < 0.05), paralleled by induction of iNOS in the 3 and 24 h samples. Prostaglandin production via COX-2 appears to mediate the development of acute inflammatory hyperaemia, but nitrergic mechanisms may supervene subsequently. COX-1 but not COX-2 contributes to the maintenance of basal blood flow in the hyperaemic joint at 24 h.</p>

Item Type:Articles
Glasgow Author(s) Enlighten ID:Ferrell, Professor William
Authors: Egan, C.G., Lockhart, J.C., Ferrell, W.R., Day, S.M., and McLean, J.S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Physiology
ISSN (Online):1469-7793
Published Online:25 January 2002

University Staff: Request a correction | Enlighten Editors: Update this record