Effect of angiotensin II on glomerular structure in streptozotocin-induced diabetic rats.
OBJECTIVE
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).


CONCLUSIONS
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.
Nicholas
Susanne B
SB
Department of Medicine, Division of Nephrology and Endocrinology, David Geffen School of Medicine at UCLA, Los Angeles, Calif., USA. sunicholas@mednet.ucla.edu
Mauer
Michael
M
Basgen
John M
JM
Aguiniga
Elsa
E
Chon
Yun
Y
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000139:chemically induced* / Q000473:pathology*; D006973:Hypertension / Q000139:chemically induced*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D013311:Streptozocin