Effects of Specific Antagonists of Angiotensin II Receptors and Captopril on Diabetic Nephropathy in Mice

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 wer...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1997, Vol.75 (1), p.59-64
Main Authors: Takashi, Yotsumoto, Takeshi, Naitoh, Ken-ichi, Shikada, Sakuya, Tanaka
Format: Article
Language:English
Subjects:
Albuminuria - chemically induced
Albuminuria - drug therapy
Albuminuria - metabolism
Angiotensin II receptor antagonist
Angiotensin Receptor Antagonists
Angiotensin-converting enzyme inhibitor
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Animals
Antihypertensive Agents - therapeutic use
Captopril - therapeutic use
Creatinine - metabolism
Diabetes Mellitus, Experimental - complications
Diabetic Nephropathies - drug therapy
Diabetic Nephropathies - etiology
Diabetic nephropathy
Disease Models, Animal
Hypertrophy - drug therapy
Imidazoles - pharmacology
Kidney Diseases - pathology
Losartan - therapeutic use
Male
Mice
Mice, Inbred Strains
Pyridines - pharmacology
Receptors, Angiotensin - therapeutic use
Streptozocin - pharmacology
Urinary albumin excretion
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Summary: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 14 and 34.6% on day 28). PD123177 (angiotensin II type 2 receptor antagonist) also attenuated the increment of UAE (24.7% on day14) 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.
ISSN:0021-5198
1347-3506
DOI:10.1016/S0021-5198(19)31347-2