P-341: Selective COX-2 inhibitors and renal injury in salt-sensitive hypertension

Hermann, Matthias ; Shaw, Sidney ; Luscher, Thomas F. ; Grone, Hermann J. ; Ruschitzka, Frank

In: American Journal of Hypertension, 2005, vol. 18, no. S4, p. 129A-129A

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    Renal safety of selective COX-2 inhibitors (coxibs) is a matter of ongoing discussion. Therefore, in the present study we examined the effects of two different coxibs, celecoxib and rofecoxib, compared to a traditional NSAID, diclofenac, and placebo in salt-sensitive hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed with NaCl enriched diet (4% NaCl) for 8 weeks. Diclofenac (DS-diclofenac), rofecoxib (DS-rofecoxib), celecoxib (DS-celecoxib) or placebo were added to chow from week 6 to 8. Immunostaining for monocytes/macrophages (ED1) and cytotoxic T-lymphocytes (CD8) was performed. In addition, renal morphology and proteinuria were assessed. COX-2 protein and mRNA were isolated from renal cortex. Untreated hypertensive animals showed preglomerular and glomerular injury including endothelial activation/proliferation, broadened adventitia, collapsing glomerulopathy, mesangial sclerosis, mesangiolysis, extracapillary proliferation, protein drops and especially high grade of glomerulosclerosis (p<0.05 vs DR-placebo) and CD8 and ED1 positive cells (p<0.01 vs DR-placebo) which was improved by celecoxib but not by diclofenac and rofecoxib. Proteinuria was observed in hypertensive animals (p<0.0001 vs DR-placebo), normalised by celecoxib (p=0.0015 vs DS-placebo) and increased by rofecoxib (p<0.05 vs DS-placebo). COX-2 protein and mRNA levels were comparable in all groups. Renal function and morphology improves after celecoxib but not after rofecoxib or diclofenac. This head-to-head comparison demonstrates differential effects of coxibs on renal morphology and function in salt-dependent hypertension