Long-term blockade of angiotensin AT1 receptors increases survival of obese Zucker rats.
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.
Janiak
Philip
P
Cardiovascular Research Department, Sanofi-Synthelabo Research, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin Cedex, Hôpital Georges Pompidou, Paris, France. philip.janiak@sanofi-aventis.com
Bidouard
Jean-Pierre
JP
Cadrouvele
Catherine
C
Poirier
Bruno
B
Gouraud
Laurent
L
Grataloup
Yoann
Y
Pierre
Françoise
F
Bruneval
Patrick
P
O'Connor
Stephen Eric
SE
Herbert
Jean-Marc
JM
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
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D013777:Tetrazoles; D000077405:Irbesartan