Involvement of angiotensin II in progression of renal injury in rats with genetic non-insulin-dependent diabetes mellitus (Wistar fatty rats).
Wistar fatty (WF) rats have a genetic predisposition to hyperglycemia, polyuria, hyperinsulinemia, hyperlipidemia, obesity and nephropathy. These phenotypic characteristics are similar to those observed in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. In this study, the effects of two types of renin-angiotensin system inhibitors, an angiotensin II type 1-receptor antagonist (AT1A) and an angiotensin I-converting enzyme inhibitor (ACEI), on renal injury in WF rats were studied during the progressive phase of diabetic nephropathy. An AT1A, candesartan cilexetil (1 mg/kg), and an ACEI, enalapril (10 mg/kg), were administered orally once a day for 12 weeks, beginning when the rats were 27-week-old and already showed diabetic nephropathy and obesity. Both drugs prevented an increase in proteinuria during the experimental period. Furthermore, after 4-week intervention, the levels of proteinuria were markedly lower in drug-treated rats. At the end of the experiment, both drugs prevented the development of glomerular lesions without affecting glucose metabolism and obesity. In conclusion, the inhibition of angiotensin II activity ameliorated both existing proteinuria and the progression of proteinuria, resulting in preservation of glomerular structure. Thus angiotensin II plays important roles in the development and the progression of nephropathy in genetically obese diabetic WF rats.
Noda
M
M
Pharmacology Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan. Noda_Masakuni@takeda.co.jp
Matsuo
T
T
Nagano-Tsuge
H
H
Ohta
M
M
Sekiguchi
M
M
Shibouta
Y
Y
Naka
T
T
Imura
Y
Y
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D008297:Male; D011506:Proteins / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D044140:Receptor, Angiotensin, Type 1; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles; D014280:Triglycerides / Q000097:blood
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011506:Proteins; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014280:Triglycerides; D000804:Angiotensin II; D004656:Enalapril; D002784:Cholesterol; D003404:Creatinine; C077793:candesartan cilexetil