title: The angiotensin receptor antagonist, irbesartan, reduces renal injury in experimental chronic renal failure.
abstract: The effects of chronic treatment with the specific AT1 angiotensin receptor antagonist, irbesartan, or the angiotensin converting enzyme inhibitor, enalapril, were assessed in uninephrectomized fawn-hooded hypertensive rats (FHH) and compared with vehicle treatment. Three days after uninephrectomy, irbesartan (240 mg/liter), enalapril (80 mg/liter) or vehicle were administered via the drinking water. Systolic blood pressure (SBP) and protein excretion rates (UprotV) were determined monthly. In rats receiving irbesartan (N = 7) and enalapril (N = 6) SBP (132 +/- 3 mm Hg and 133 +/- 6, respectively) was essentially normalized at 12 weeks when compared with vehicle (169 +/- 6 mm Hg (N = 6); all comparisons were P < 0.05 by ANOVA). Similarly, proteinuria was lower in irbesartan (44 +/- 12 mg/day) and enalapril (19 +/- 2) groups versus vehicle (123 +/- 10 mg/day). Treatment with both drugs was associated with marked reduction in glomerulosclerosis at 12 weeks (both < 5% vs. vehicle, 43 +/- 9%) without effect on glomerular volume. In identically prepared rats, glomerular capillary hydraulic pressure (PGC, estimated from stop-flow pressure, Psf) was lower in FHH receiving irbesartan (58 +/- 1 mm Hg, N = 6) or enalapril (54 +/- 2, N = 6) than in vehicle-treated rats, in whom PGC was greatly elevated (68 +/- 2 mm Hg; N = 7). Despite this, GFR and single nephron GFR were well maintained. These data support a critical role for AT1 receptor-mediated, angiotensin-dependent processes in the pathogenesis of hypertension in FHH, and further implicate elevated PGC as a major determinant of glomerular injury in this model.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: F
authors.initials: F
authors.lastname: Ziai
authors.forename: M
authors.initials: M
authors.lastname: Ots
authors.forename: A P
authors.initials: AP
authors.lastname: Provoost
authors.forename: J L
authors.initials: JL
authors.lastname: Troy
authors.forename: H G
authors.initials: HG
authors.lastname: Rennke
authors.forename: B M
authors.initials: BM
authors.lastname: Brenner
authors.forename: H S
authors.initials: HS
authors.lastname: Mackenzie
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology*; D000077405:Irbesartan; D007676:Kidney Failure, Chronic / Q000188:drug therapy; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology; D009392:Nephrectomy; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; D000077405:Irbesartan