Key result
Captopril treatment significantly reduced intrarenal angiotensin II levels (13.98 vs 25.39 pg/gm, p<0.01) and reversed the expression of nephrin and fibrogenic molecules in a rat model of type 2 diabetes.
Why the study?
Does captopril prevent the progression of nephropathy in a Zucker Obese rat model of type 2 diabetes?
Does captopril prevent the progression of nephropathy in a Zucker Obese rat model of type 2 diabetes?
In a rat model of type 2 diabetes, ACE inhibition with captopril prevents nephropathy progression by reversing ANG II-mediated decreases in nephrin and increases in fibrogenic molecules.
Answers are grounded in this paper and cite their sources.
Cautions against clinical extrapolation from this rat model; leaves open mechanistic and translational studies in diabetic nephropathy.
Diabetic nephropathy characterized by proteinuria and sclerosis is the leading cause of renal failure, but its mechanisms are not well understood. Zucker Obese (ZO) rat model of obesity, insulin resistance, and hypertension has been used to study nephropathy. We hypothesize that chronically elevated intrarenal angiotensin II (ANG II) down-regulates nephrin, a key slit-pore protein and up-regulates fibrogenic molecule transforming growth factor (TGFbeta1) and thus result in progression of nephropathy in type 2 diabetes. Untreated or angiotensin converting enzyme (ACE) inhibitor, captopril, treated ZO and control Lean (ZL) rats were used to measure intrarenal levels of ANG II, glomerular nephrin, TGFbeta1, collagen and fibronectin with age using radioimmunoassay, RT-PCR and immunoblot techniques. Progression of nephropathy was established by measuring proteinuria and sclerosis. ZO rats developed obesity, hyperglycemia, hyperinsulinimia, increase in intrarenal ANG II and proteinuria. Expression of glomerular nephrin decreased while expression of TGFbeta1 and matrix components increased in ZO rats. Captopril treatment prevented increase in intrarenal ANG II, and reversed expression of nephrin, TGFbeta1, collagen and fibronectin. We conclude that in this model of type 2 diabetic nephropathy, chronically elevated intrarenal ANG II causes proteinuria via decrease in nephrin and glomerulosclerosis via TGFbeta1 mediated increase in matrix component.
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Ram Sharma (2006) studied Diabetic nephropathy (Type 2 diabetes). Captopril vs. Untreated Zucker Obese rats was evaluated on Intrarenal ANG II concentration at 21 weeks (pg/gm of kidney) (p=<0.01). Captopril treatment significantly reduced intrarenal angiotensin II levels (13.98 vs 25.39 pg/gm, p<0.01) and reversed the expression of nephrin and fibrogenic molecules in a rat model of type 2 diabetes.
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