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(Hypertension. 2000;36:233.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Effect of Antihypertensive Therapy on Renal Injury in Type 2 Diabetic Rats With Hypertension
From the Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark.
Correspondence to A.S. Reddi, MD, PhD, Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 S Orange Ave, Newark, NJ 07103. E-mail reddias{at}umdnj.edu
Abstract—In a previous study, we
demonstrated that doxazocin (DZN), an 
1-adrenergic
blocker, prevented proteinuria in streptozotocin diabetic rats. In this
study, we investigated whether DZN would lower established proteinuria
by improving glomerular sclerosis in spontaneously
hypertensive corpulent rats with type 2 diabetes mellitus. DZN
treatment was compared with treatment with
angiotensin-converting enzyme inhibitor,
lisinopril (LIS) alone, and DZN in combination with LIS.
Combination therapy was used to examine any additive effect of either
drug alone in the reduction of proteinuria and glomerular
sclerosis. Both male and female rats age 6 months with established
proteinuria were used. The rats were allocated randomly to 1 of 4
groups: untreated, DZN treated, LIS treated, or a combination of DZN
and LIS treatment. Drug treatment was continued for 16 weeks. The
results show that (1) either drug alone or in combination significantly
lowered systolic blood pressure; (2) DZN, LIS, or combination
therapy reduced albuminuria at 16 weeks of treatment from
baseline by 38.61±5.77%, 30.70±4.21%, and 42.17±4.77% (mean±SE),
respectively. No difference in albuminuria was observed
among the 3 groups of rats; (3) the fractional mesangial
area, which was 20.55±3.77% in untreated rats, was significantly
reduced to 11.18±1.32% in DZN-treated rats, with a further reduction
to 8.72±0.64% in LIS-treated rats and to 3.48±0.35% in rats treated
with DZN+LIS; and (4) DZN but not LIS significantly improved plasma
glucose levels in spontaneously hypertensive corpulent rats (untreated
21.06±0.97 mmol/L versus DZN treated 15.81±0.93 mmol/L or
DZN+LIS treated 17.38±1.10 mmol/L; P<0.025 to
0.005). Thus, the data suggest that 16-week treatment with either DZN
or LIS improves established proteinuria and glomerular
sclerosis, but combination therapy is superior to either DZN or LIS
alone in preventing glomerular sclerosis in type 2 diabetic
rats with hypertension.
Key Words: diabetic nephropathy • rats, spontaneously hypertensive • adrenergic receptor blocker • antihypertensive agents • angiotensin-converting enzyme inhibitors • albuminuria • glomerulosclerosis
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