Abstract-We have previously demonstrated that antihypertensive treatment with doxazosin (DZN), an ␣-adrenergic blocker, and lisinopril (LIS), an ACE inhibitor, reverse glomerular sclerosis in corpulent spontaneously hypertensive rats with type 2 diabetes. In this study, we examined the effects of the above-mentioned antihypertensive drugs alone and in combination on the structure of interlobular and arcuate arteries in these rats. Both male and female rats aged 6 months were treated with antihypertensive drugs for 16 weeks. Various structural parameters were evaluated by light microscopy, with the use of digital image analysis, in kidney sections stained with periodic acid-Schiff. Systolic blood pressure was significantly lower in treated than in untreated rats. Untreated diabetic rats had a significantly higher media/lumen ratio (smaller luminal diameter) of both arteries compared with the ratio in treated rats (for interlobular artery, 0.72Ϯ0. . Antihypertensive treatment caused significant increases in total arterial cross-sectional area, internal and external diameters, luminal and medial cross-sectional area, and medial thickness in both interlobular and arcuate arteries. The improvement in arterial structure after antihypertensive treatment was due to remodeling and growth of the vessels. Both DZN and LIS were equally efficacious, and combination therapy had no additive or synergistic effect.

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 38.61Ϯ5.77%, 30.70Ϯ4.21%, and 42.17Ϯ4.77% (meanϮSE), respectively. No difference in albuminuria was observed among the 3 groups of rats; (3) the fractional mesangial area, which was 20.55Ϯ3.77% in untreated rats, was significantly reduced to 11.18Ϯ1.32% in DZN-treated rats, with a further reduction to 8.72Ϯ0.64% in LIS-treated rats and to 3.48Ϯ0.35% in rats treated with DZNϩLIS; and (4) Key Words: diabetic nephropathy Ⅲ rats, spontaneously hypertensive Ⅲ adrenergic receptor blocker Ⅲ antihypertensive agents Ⅲ angiotensin-converting enzyme inhibitors Ⅲ albuminuria Ⅲ glomerulosclerosis D iabetes mellitus is the leading cause of end-stage renal disease in the United States. 1 Both type 1 and type 2 diabetic patients are at risk for the development of nephropathy because of hyperglycemia and its consequences. Morphologically, either diffuse or selective expansion of the mesangial matrix, which causes obliteration of the capillary lumen and loss of filtration surface area, is characteristic of diabetic nephropathy. Clinically, microalbuminuria, which is defined as urinary albumin excretion of 30 to 300 mg/d, is the hallmark of diabetic nephropathy. Several studies have shown that microalbuminuria can predict the later development of diabetic nephropathy in both types of diabetic subjects. 2,3 Prevention of microalbuminuria by good glycemic control was found to preserve renal function and to delay the progression of diabetic nephropathy in animals and human subjects. 4 -6 In addition to hyperglycemia, systemic hypertension can aggravate diabetic nephropathy. Several studies have shown that control of hypertension not only improves proteinuria but also delays the progression of diabetic nephropathy. 7-9 Among antihypertensive drugs, the angiotensinconverting enzyme (ACE) inhibitors were found to be therapeutically more efficacious in protecting the kidney than other groups of antihypertensive drugs. 2,10 -13 However, some calcium blockers, 14 -16 ␣ 1 -b...

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