Cyclooxygenase-2 inhibitor blocks expression of mediators of renal injury in a model of diabetes and hypertension1 (original) (raw)

2002, Kidney International

group had an index of 0.06 Ϯ 0.01, the diabetic group was Cyclooxygenase-2 inhibitor blocks expression of mediators of 2.7 Ϯ 0.04 and the treated group was 0.6 Ϯ 0.03 (P Ͻ 0.0001 renal injury in a model of diabetes and hypertension. compared to the diabetic group). Background. We previously reported that renal cortical Conclusions. These results suggest that in an experimental cyclooxygenase (COX-2) expression increased following subtomodel of diabetes and hypertension, inhibition of COX-2 extal nephrectomy, and chronic treatment with a selective COX-2 inhibitor, SC58236, reduced proteinuria and retarded the depression decreases potential mediators of glomerular and tubuvelopment of glomerulosclerosis. The present studies were delointerstitial injury and also decreases biochemical, functional signed to examine the effects of COX-2 inhibition in a model and structural markers of renal injury. of diabetic nephropathy. Methods. Rats were divided into three groups: control, diabetic (streptozotocin-induced diabetic animals with superim-Previous studies have suggested that prostaglandins posed DOCA/salt hypertension; right nephrectomy and DOCA treatment), and treated (administration of the selective COX-2 may be involved in the development of diabetic nephropinhibitor, SC58236, to a subset of diabetic/DOCA/salt rats). athy. Increased urinary and glomerular prostaglandin Insulin was administered to maintain blood glucose in the 200 production has been reported in experimental models to 300 mg/dL range. of diabetes [1-5]. Prostaglandins have been implicated Results. Systolic blood pressure in the two diabetic groups as mediators of the alterations in renal hemodynamics was elevated within one week and remained elevated until sacrifice at six weeks (control, 108 Ϯ 2 mm Hg; diabetic, 158 Ϯ in early diabetes [3, 6, 7], and of increased mesangial 4 mm Hg; treated, 156 Ϯ 7 mm Hg). When measured at six 1 See Editorial by Zatz and Fujihara, p. 1091. macula densa cells and to a subset of medullary interstitial cells in the papilla [13]. In chronically salt depleted