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(Hypertension. 1997;30:1232-1237.)
© 1997 American Heart Association, Inc.

Articles

Perindopril Ameliorates Glomerular and Renal Tubulointerstitial Injury in the SHR/N-Corpulent Rat

Manuel T. Velasquez; John S. Striffler; Andrew A. Abraham; Otho E. Michaelis, IV¹; Elizabeth Scalbert; Nancy Thibault

From the Departments of Medicine and Pathology, George Washington University Medical Center, Washington, DC; Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Beltsville, Md; University of Maryland, College Park, Md; and Cardiorespiratory Department, Institut De Recherches Internationales Servier & Compagnie-Developpement, Paris, France.

Correspondence to Manuel T. Velasquez, MD, Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, 2150 Pennsylvania Ave, NW, Washington, DC 20037.

Abstract We compared the effects of long-term treatment with the angiotensin-converting enzyme inhibitor perindopril and triple therapy (hydrochlorothiazide, reserpine, and hydralazine) on the metabolic and renal features in the SHR/N-corpulent (cp) rat, a genetic model of non–insulin-dependent diabetes mellitus and hypertension. Obese male SHR/N-cp rats (4 to 6 weeks old) were fed a 54% carbohydrate diet containing 18% sucrose and 36% starch. After 2 months on the diet, rats were assigned to one of three groups: one group (n=8) received perindopril (PE); the second group (n=8) received triple therapy (TT); and the third group (n=8) did not receive therapy. Treatment was maintained for 3 to 4 months. Body weight, food intake, and fasting levels of serum glucose and insulin did not differ among the three groups. Control rats exhibited progressive proteinuria in parallel with the rise in systolic blood pressure (SBP). Both PE and TT equally lowered SBP to normal levels and reduced proteinuria in treated rats. However, the reduction of proteinuria was greater and more sustained with PE than with TT (P<.05), whereas the effect of TT on proteinuria was delayed. Plasma renin activity was increased in PE and TT rats compared with control rats (P<.02). Semiquantitative analysis of renal lesions showed that the percentage of glomeruli with mesangial expansion and sclerosis and the tubulointerstitial score (an index of severity of tubulointerstitial lesions, namely tubular atrophy, inflammatory cellular infiltrates, and interstitial fibrosis) was reduced in both PE and TT rats. However, the reduction of glomerulosclerosis and tubulointerstitial lesions was greater in PE than in TT rats (P<.01). The percentage of glomerular sclerosis was positively correlated with the severity score of tubulointerstitial lesions (r=.60, P<.01). We conclude that PE is more effective than TT in halting the progression of proteinuria in the SHR/N-cp rat with non–insulin-dependent diabetes mellitus and hypertension. The antiproteinuric effect of PE is associated with significant reduction in glomerulosclerosis and tubulointerstitial lesions, independent of the effect of treating hypertension.

Key Words: glomerulosclerosis • rats, inbred SHR • angiotensin-converting enzyme inhibition • proteinuria • diabetes mellitus, non–insulin-dependent • renal tubulointerstitium

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