Effects of cicaprost and fosinopril on the progression of rat diabetic nephropathy

Abstract

We have studied the effects of chronic therapy with cicaprost (a PGI2 analog), fosinopril (a converting enzyme inhibitor), and the combination of both drugs on the progression of experimental diabetic nephropathy. Uninephrectomized streptozotocin-induced diabetic rats were maintained for 8 months with plasma glucose between 13.7 and 22.0 mmol/L to hasten renal damage. Systemic and renal parameters were measured periodically, and at sacrifice structural and morphometrical renal studies were performed to evaluate diabetic injury. Control rats exhibited characteristic features of this model, such as high blood pressure and plasma creatinine and urinary albumin excretion, together with prominent alterations in the kidney (renal and glomerular hypertrophies, mesangial matrix expansion, and tubular alterations). The three therapies attenuated equivalently the progression of diabetic renal injury, as estimated by lower urinary albumin excretion, renal and glomerular hypertrophies, and a better renal architectural preservation. No synergistic action was appreciated with the combined therapy. However, renal preservation achieved with cicaprost was not linked to reductions in systemic blood pressure, whereas in the groups treated with fosinopril the hypotensive effect of this drug could have contributed to the positive outcome of the therapy. Therefore, nephroprotection exerted by this PGI2 analog in this model seems more related to the derangement of renal local mechanisms than to systemic blood pressure control. Finally, the possibility that an impaired prostacyclin synthesis or bioavailability is involved in the pathogenesis of the diabetic nephropathy in this model underlies our results.

Intravenous Administration of Hepatocyte Growth Factor Gene Ameliorates Diabetic Nephropathy in Mice

“…Of interest, our findings that HGF ameliorates DN are independently confirmed by two recent reports with a similar conclusion (34,35). The present study used a UNx-diabetic model in an effort to accelerate the development and progression of DN in mice (24,25). In our pilot experiments, no significant renal fibrosis was observed after 6 mo in a standard STZ diabetic mouse model (data not shown).…”

“…For evaluating the effects of exogenous HGF on diabetic kidney, a uninephrectomized (UNx) diabetic model was used (24,25). Mice underwent UNx 1 wk before streptozotocin (STZ; Sigma, St. Louis, MO) injection (day Ϫ7).…”

Smoking in diabetic nephropathy: sparks in the fuel tank?

“…In particular, the use of a different class of drugs, such as ACE inhibitors captopril, lisinopril, fosinopril, benazapril and quinapril, and AT-Ⅰ receptor blockers, such as losartan, olmesartan and irbesartan, have been observed in numerous experimental and clinical studies to have therapeutic potential in the treatment of diabetic nephropathy [69][70][71][72][73][74][75][76][77] . Captopril was the first drug approved by Food and Drug Administration in the nineties for the treatment of diabetic nephropathy [48] .…”

Clinical and Experimental Evidence for Prevention of Acute Renal Failure Induced by Radiographic Contrast Media

“…Both the immunohistochemical study using polyclonal antibody raised against IP receptor and in situ hybridization have demonstrated that IP receptor distributes to the glomerular cells, endothelial cells, distal tubules, and collecting ducts in human kidneys (126). Prostacyclin is reported to attenuate the diabetic renal injury induced by streptozotocin in unilateral nephrectomized rats (127) and ischemia / reperfusion-induced renal injury in dogs (128). Although the protective effect of prostacyclin is considered to be due primarily to the vasodilatory action, direct protective action on renal epithelial cells is also shown in the in vitro model of hypoxia / reoxygenationinduced injury in cultured rat proximal renal tubular cells (129).…”