title: Losartan-hydrochlorothiazide association promotes lasting blood pressure normalization and completely arrests long-term renal injury in the 5/6 ablation model.
abstract: The possible long-term renoprotective effects of treatment with thiazides, either as monotherapy or associated with renin-angiotensin suppressors, have not been assessed. We investigated the effect of hydrochlorothiazide (H), alone or combined with losartan (L), in the 5/6 renal ablation model (Nx). Adult male Munich-Wistar rats underwent Nx, remaining untreated for 1 mo. At this time, functional and morphological studies were performed in 21 rats (group Nx(pre)). The remaining rats were distributed among groups: Nx, no treatment; Nx+L, receiving L, 50 mg kg(-1) day(-1) in the drinking water; Nx+H, receiving H, 6 mg kg(-1) day(-1) in drinking water; and Nx+L+H, receiving both L and H as described. At 30 days of treatment, systemic and glomerular pressures were markedly elevated in group Nx. Both H and L attenuated hypertension, whereas combined L+H treatment completely normalized both pressures. Eight months after Nx, mortality approached 70% in untreated rats, whereas severe albuminuria, hypertension, glomerulosclerosis, and interstitial expansion were observed. H and L attenuated, but did not prevent, mortality, hypertension, and renal injury. Combined L+H treatment completely prevented mortality, normalized albuminuria and blood pressure, and arrested renal injury at levels found 1 mo after ablation, despite the unusually long period of observation. Combined L+H treatment may represent an effective therapeutic alternative to prevent progression of chronic nephropathies.
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Clarice Kazue
authors.initials: CK
authors.lastname: Fujihara
authors.forename: Denise M A C
authors.initials: DM
authors.lastname: Malheiros
authors.forename: Roberto
authors.initials: R
authors.lastname: Zatz
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics / Q000627:therapeutic use*; D004357:Drug Synergism; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000473:pathology; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D013623:Tail / Q000098:blood supply
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004232:Diuretics; D006852:Hydrochlorothiazide; D019808:Losartan