Irbesartan lowers blood pressure and ameliorates renal injury in experimental non-insulin-dependent diabetes mellitus.
In the present study, we investigated the effects of the angiotensin (Ang) II receptor antagonist, irbesartan, on blood pressure and renal structural injury in obese Zucker rats (OZR), an experimental model of non-insulin-dependent diabetes mellitus (NIDDM). Twenty-six-week-old OZR with established renal disease were administered either low-dose (15 mg/kg) or high-dose (50 mg/kg) irbesartan in the drinking water for a period of 18 weeks. Irbesartan caused dose-related reductions in blood pressure, and reduced by 47 to 60% the percent of glomeruli with sclerosis at 44 weeks of age (P < 0.05). In addition, irbesartan at the higher dose reduced the tubulointerstitial injury score at 44 weeks by approximately 75% (P < 0.05). By contrast, irbesartan did not significantly reduce albuminuria in OZR. The results of the present study demonstrate that the Ang II receptor antagonist irbesartan can reduce blood pressure and ameliorate glomerular and tubulointerstitial injury in an experimental model of NIDDM.
O'Donnell
M P
MP
Department of Medicine, Hennepin County Medical Center, Minneapolis, USA.
Crary
G S
GS
Oda
H
H
Kasiske
B L
BL
Powell
J R
JR
Keane
W F
WF
D000419:Albuminuria / Q000188:drug therapy / Q000652:urine; 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*; D003864:Depression, Chemical; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000473:pathology; D000077405:Irbesartan; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D013777:Tetrazoles / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan