期刊
AMERICAN JOURNAL OF NEPHROLOGY
卷 24, 期 5, 页码 549-556出版社
KARGER
DOI: 10.1159/000082001
关键词
angiotensin II; infusion; albumin excretion rate; streptozotocin; rat; morphometry
资金
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK030254, R37DK030254] Funding Source: NIH RePORTER
- NIDDK NIH HHS [DK3025416, DK07789] Funding Source: Medline
Background/Aims: The streptozotocin (STZ)-induced diabetic rat is a widely used animal model of human diabetic nephropathy. In this model, diabetic nephropathy progresses without significant elevation in blood pressure. Therefore, studies have examined the effect of hypertension in STZ spontaneously hypertensive rats (SHR). This study investigated angiotensin II (Ang II)induced hypertension in diabetic nephropathy in the STZ-diabetic rat independent of deleterious genetic effects in SHR. Methods: Animals were divided as follows: nondiabetic controls (ND; n = 18); diabetic ( STZ: 65 mg/ kg; n = 16); Ang II-induced hypertensive ND ( Ang II: 120 ng/kg/min; n = 9), and hypertensive diabetic rats ( n = 18). Systolic blood pressure was measured by the tailcuff method prior to STZ injection and then weekly. After 3 months, plasma creatinine, and 24-hour urine albumin and creatinine were measured and kidneys harvested for morphometry. Results: Ang II infusion increased systolic blood pressure in diabetic and ND rats. When combined with diabetes, Ang II increased albumin excretion rate 14-fold, p < 0.05), plasma creatinine ( 1.5-fold, p < 0.005) worsened creatinine clearance (37%, p < 0.002) and increased glomerular basement membrane width (1.2-fold, p < 0.0001). Conclusion: Ang II caused moderate hypertension and accelerated diabetic nephropathy and glomerular structural changes. The Ang II-infused STZ-diabetic rat is an excellent model to study the deleterious glomerular effects of hypertension on diabetes independent of genetic traits. Copyright (C) 2004 S. Karger AG, Basel.
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