Effects of angiotensin receptor blocker on oxidative stress and cardio-renal function in streptozotocin-induced diabetic rats.
The important role of renin-angiotensin-aldosterone system blockade in the treatment of diabetes-induced cardiomyopathy and nephropathy has been clearly established. The present study examined the effect of angiotensin II type 1 receptor blocker (ARB) losartan on oxidative stress and cardio-renal function in streptozotocin (STZ)-induced diabetic rats. Losartan treatment resulted in improvement of myocardial function and suppressed cardiac and renal fibrosis compared with the diabetic group. Losartan treatment also down-regulated transforming growth factor-beta1 expression and attenuated the increased expression levels of p22(phox) and Nox4. Blood urea nitrogen (BUN) and urinary protein levels were increased significantly in the diabetic group. Losartan treatment significantly reduced proteinuria but not BUN level. Moreover, the elevated level of malondialdehyde in both heart and kidney were significantly reduced in the losartan-treated group compared with the diabetic group. These results provided evidence that oxidative stress plays a major role in diabetic rats induced by STZ, and treatment with the ARB might be beneficial for preventing the development and progression of diabetic disease.
Arozal
Wawaimuli
W
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Watanabe
Kenichi
K
Veeraveedu
Punniyakoti Thanikachalam
PT
Ma
Meilei
M
Thandavarayan
Rajarajan Amirthalingam
RA
Suzuki
Kenji
K
Tachikawa
Hitoshi
H
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D047228:Angiotensin II Type 1 Receptor Blockers; D008315:Malondialdehyde; D013311:Streptozocin; D019808:Losartan