title: Long-term blockade of angiotensin AT1 receptors increases survival of obese Zucker rats.
abstract: Despite the well-documented effect of irbesartan, an angiotensin AT1 receptor antagonist, on diabetic nephropathy, its effect on mortality related to multiple metabolic risk factors is unknown. To address this question, obese fa/fa Zucker rats were submitted to a 13-month treatment by irbesartan (30 mg/kg/day p.o.). Vehicle-treated obese fa/fa Zucker rats exhibited an important mortality (72%), which was markedly reduced by irbesartan (22%, P<0.05). Mortality in control lean fa/+ rats attained 12%. Irbesartan diminished the elevation in urinary protein excretion, plasma creatinine and urea nitrogen levels, and reduced the extent of glomerular and tubulo-interstitial lesions together with a reduction of urinary monocyte chemoattractant protein-1 excretion in fa/fa Zucker rats. Irbesartan treatment prevented the rise in plasma total cholesterol, triglycerides and glucose levels, and partially corrected low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio in fa/fa Zucker rats. Therefore, prolonged irbesartan treatment preserves renal function and metabolic profile, and substantially increases survival in obese fa/fa Zucker rats.
authors.affiliation: Cardiovascular Research Department, Sanofi-Synthelabo Research, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin Cedex, Hôpital Georges Pompidou, Paris, France. philip.janiak@sanofi-aventis.com
authors.forename: Philip
authors.initials: P
authors.lastname: Janiak
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bidouard
authors.forename: Catherine
authors.initials: C
authors.lastname: Cadrouvele
authors.forename: Bruno
authors.initials: B
authors.lastname: Poirier
authors.forename: Laurent
authors.initials: L
authors.lastname: Gouraud
authors.forename: Yoann
authors.initials: Y
authors.lastname: Grataloup
authors.forename: Françoise
authors.initials: F
authors.lastname: Pierre
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Stephen Eric
authors.initials: SE
authors.lastname: O'Connor
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D007328:Insulin / Q000097:blood; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D013777:Tetrazoles; D000077405:Irbesartan