title: Effects of specific antagonists of angiotensin II receptors and captopril on diabetic nephropathy in mice.
abstract: 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.
authors.affiliation: Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd., Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yotsumoto
authors.forename: T
authors.initials: T
authors.lastname: Naitoh
authors.forename: K
authors.initials: K
authors.lastname: Shikada
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
mesh_terms: 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
chemical_list: 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