Effects of Specific Antagonists of Angiotensin II Receptors and Captopril on Diabetic Nephropathy in Mice
Takashi Yotsumoto, Takeshi Naitoh, Ken-ichi Shikada and Sakuya Tanaka
Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd., 1470, Shiraoka, Minamisaitama, Saitama 349-02, Japan
Abstract: We investigated whether angiotensin II was involved with diabetic nephropathy in the mouse model. Twelve days after streptozotocin (STZ) injection, the urinary albumin excretion (UAE) level was increased by 118% of the baseline value. On days 21, 28, 35 and 42 after STZ injection, the UAE levels were significantly increased compared with the level at day 12. A marked elevation of creatinine clearance and diabetic-induced renal hypertrophy were also observed on day 49 after STZ injection. The 35-day treatments of captopril and Dup 753 (angiotensin II type 1 receptor antagonist) significantly attenuated the increment of UAE levels (26.4% on day l4 and 34.6% on day 28). PD123177 (angiotensin II type 2 receptor antagonist) also attenuated the increment of UAE (24.7% on day l4) at the dose of 150 mg/kg. Furthermore, Dup 753 partially prevented diabetic-induced renal hypertrophy. These results suggest that angiotensin II type 2 receptor as well as type 1 receptor may be involved in the development of diabetic nephropathy in the STZ-induced diabetic mice, and these mice are beneficial models of early diabetic nephropathy.
Keywords: Diabetic nephropathy, Urinary albumin excretion, Angiotensin-converting enzyme inhibitor, Angiotensin II receptor antagonist