Effect of Angiotensin II on Glomerular Structure in Streptozotocin-Induced Diabetic Rats

Vol. 24, No. 5, 2004

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Original Report: Laboratory Investigation

Effect of Angiotensin II on Glomerular Structure in Streptozotocin-Induced Diabetic Rats
Susanne B. Nicholas^a, Michael Mauer^d, John M. Basgen^d, Elsa Aguiniga^b, Yun Chon^c

^aDepartment of Medicine, Divisions of Nephrology and Endocrinology, Diabetes, and Hypertension,
^bDepartment of Medicine, Division of Nephrology, and
^cDivision of Epidemiology, David Geffen School of Medicine at UCLA, LosAngeles, Calif., and
^dDepartment of Pediatrics, Division of Nephrology, University of Minnesota, Minneapolis, Minn., USA

Address of Corresponding Author

Am J Nephrol 2004;24:549-556 (DOI: 10.1159/000082001)

Key Words

Angiotensin II
Infusion
Albumin excretion rate
Streptozotocin
Rat
Morphometry

Abstract

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 tail-cuff 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.

Author Contacts

Susanne B. Nicholas, MD, PhD
900 Veteran Avenue, Suite 24-130
Los Angeles, CA 90095 (USA)
Tel. +1 310 794 7555, Fax +1 310 794 7654
E-Mail sunicholas@mednet.ucla.edu

Article Information

Received: July 15, 2004
Accepted: October 6, 2004
Published online: November 10, 2004
Number of Print Pages : 8
Number of Figures : 3, Number of Tables : 2, Number of References : 28

Medline Abstract (ID 15539791)

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