Captopril Reduces Interstitial Renal Fibrosis and Preserves More Normal Renal Tubules in Neonatal Dogs with Partial Urethral Obstruction: A Preliminary Study

Abstract

Purpose: Chronic renal damage due to tubulointerstitial fibrosis is one of several complications of posterior urethral valves in a significant number of children. As activation of the renin-angiotensin system plays an important role in this injury, we conducted this study to investigate whether administration of captopril reduced renal fibrosis in an experimental model using partial urethral obstruction (PUO) in neonatal dogs. Material and Methods: Experimental PUO was induced in all pups. These animals were then divided into two groups: in the first group (experimental), captopril 35 mg/kg/day, dissolved in drinking water, was administered for 6 weeks. The second group (positive control) did not receive any treatment. After 6 weeks all dogs underwent left nephrectomy. Volume fraction and absolute volume of the histological kidney parameters, i.e., normal glomerulus, normal tubule, vessels, degenerated glomerulus, degenerated tubule, fibrous tissue, were estimated using modern unbiased stereological methods. Results: The absolute volume of interstitial fibrosis was lower in the experimental group (PUO with captopril treatment) (∼73%; p < 0.008) in comparison with positive control animals (PUO with no treatment). The mean absolute volume of normal tubules in the experimental group was more than the positive control group (∼33%, p < 0.008). The mean absolute volume of normal and degenerated glomerulus, vessels and degenerated tubule did not show a significant difference between the two groups. Conclusion: Administration of captopril decreases interstitial renal fibrosis and preserves renal tubules in neonatal dogs with PUO.

Inhibition of angiotensin‐converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin‐angiotensin system

“…Of interest, after 2 weeks of fracture healing, the periosteal callus of perindopriltreated animals showed less fibrous tissue compared with controls. Different studies have shown that the RAS contributes to fibrogenesis in a variety of organs like the heart, vascular wall, pancreas, kidney and liver (Kuno et al, 2003;Sun and Weber, 2003;Ikura et al, 2005;Morihara et al, 2006;Shirazi et al, 2007). Accordingly, the reduced fibrous tissue in the periosteal callus area of perindopril-treated animals is compatible with the results of other studies, which have shown reduced fibrous tissue formation after blockade of the RAS (Yoshiji et al, 2007).…”

Angiotensin II and Its Role in Tubular Epithelial to Mesenchymal Transition Associated with Chronic Kidney Disease

“…For example, in neonatal dogs with partial urethral obstruction [Shirazi et al, 2007], in the obstructed kidney of mice after unilateral ureteral obstruction (UUO) [Schanstra et al, 2002], bromoethylamine induced renal fibrosis [Garber et al, 1998], and in rats with subtotal nephrectomy [Gilbert et al, 1999], ACE inhibition reduced the severity of renal damage. Similarly, treatment with AT1 receptor antagonists attenuated tubulointerstitial fibrosis experimental models of diabetic nephropathy [Bolos et al, 2003], UUO [Ishidoya et al, 1995;Shirazi et al, 2007], subtotal (5/6) nephrectomy [Yu et al, 2000] and chronic cyclosporin nephropathy [Pichler et al, 1995].…”

The Kidney from Prenatal to Adult Life: Perinatal Programming and Reduction of Number of Nephrons during Development

“…Moreover, subsequent to completion of nephrogenesis, angiotensin receptor blockades (ARBs) prevented interstitial and glomerular cell apoptosis in newborn pigs with unilateral ureteral obstruction [101]. Finally, ACE inhibitors decreased interstitial renal fibrosis and preserved renal tubules in newborn dogs with partial urethral obstruction [102]. …”