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Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis

¹Mucosal Inflammation Research Group and ²Smooth Muscle Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, Canada; and ³Microcirculation and Lymphology Laboratory, Department of Anatomy, School of Medicine, Flinders University, Adelaide, South Australia

Submitted 6 February 2006 ; accepted in final form 27 April 2006

The ability of the lymphatic system to actively remove fluid from the interstitium is critical to the resolution of edema. The response of the lymphatics to inflammatory situations is poorly studied, so we examined mesenteric lymphatic contractile activity in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) model of guinea pig ileitis, a well-accepted animal model of intestinal inflammation, by videomicroscopy in vivo and in vitro 1, 3, and 6 days after induction of ileitis. Lymphatic function (diameter, constriction frequency, amplitude of constrictions, and calculated stroke volume and lymph flow rate) of isolated vessels from TNBS-treated guinea pigs were impaired compared with sham-treated controls. The dysfunction was well correlated with the degree of inflammation, with differences reaching significance (P < 0.05) at the highest inflammation-induced damage observed at day 3. In vivo, significantly fewer lymphatics exhibited spontaneous constrictions in TNBS-treated than sham-treated animals. Cyclooxygenase (COX) metabolites were suggested to be involved in this lymphatic dysfunction, since application of nonselective COX inhibitor (10 µM indomethacin) or a combination of COX-1 and COX-2 inhibitors (1 µM SC-560 and 10 µM celecoxib) markedly increased constriction frequency or induced them in lymphatics from TNBS-treated animals in vivo and in vitro. The present results demonstrate that lymphatic contractile function is altered in TNBS-induced ileitis and suggest a role for prostanoids in the lymphatic dysfunction.

inflammatory bowel disease; inflammation; lymph drainage; indomethacin

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