Selective
cyclooxygenase-2 (COX-2) inhibitors have anti-inflammatory activity and reduce
proteinuria in experimental
membranous glomerulonephritis. Antiangiogenic properties of
COX-2 inhibitors were recently reported. Whether these properties are relevant to the glomerular healing process in inflammatory glomerular diseases was investigated. For evaluation of the effects of selective
COX-2 inhibitors on the glomerular healing process in a rat model of mesangioproliferative
glomerulonephritis (induced by
anti-Thy 1.1 antibody), a selective
COX-2 inhibitor (
rofecoxib or
celecoxib) or vehicle was administered daily from day 1 after disease induction until
euthanasia on day 6. Additional nephritic rats were treated with
rofecoxib or vehicle from day 1 to day 10 and were monitored until day 28. Selective COX-2 inhibition led to significant increases in mesangiolysis (up to +71%) on days 2 and 6 and in
albuminuria (up to 3.1-fold) on day 6. This augmentation of glomerular capillary damage was associated with rarefaction of glomerular endothelial cells, whereas the proliferation and activation of mesangial cells were not affected. No significant effects on the glomerular influx of polymorphonuclear neutrophils or the infiltration and proliferation of monocytes/macrophages at day 2 were noted. These effects were independent of systemic hemodynamic features, because
rofecoxib did not affect systolic BP on day 2 or 5. Nephritic rats treated with
rofecoxib for 10 d demonstrated persistent glomerular injury at day 28, as indicated by increased
albuminuria (10-fold) and mesangial
type IV collagen deposition (+24%). In normal rats, 5-d administration of
rofecoxib failed to induce
albuminuria or morphologic renal damage. In conclusion, selective
COX-2 inhibitors impair glomerular capillary repair after mesangiolysis in rats with anti-Thy 1.1
glomerulonephritis. These data suggest that selective
COX-2 inhibitors should be used with caution among patients with inflammatory endocapillary glomerular disorders.