Effects of specific antagonists of angiotensin II receptors and captopril on diabetic nephropathy in mice.
We investigated whether angiotension 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 day 14) 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.
Yotsumoto
T
T
Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd., Saitama, Japan.
Naitoh
T
T
Shikada
K
K
Tanaka
S
S
D000419:Albuminuria / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D006984:Hypertrophy / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology; D007674:Kidney Diseases / Q000473:pathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D013311:Streptozocin / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; C066253:PD 123177; D013311:Streptozocin; D002216:Captopril; D003404:Creatinine; D019808:Losartan