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Annals of Clinical & Laboratory Science 35:54-65 (2005)
© 2005 Association of Clinical Scientists

Progression of Renal Damage in the Obese Zucker Rat in Response to Deoxycorticosterone Acetate-Salt-Induced Hypertension

Ryan G. Morrison1, A. Betts Carpenter2, Van L. Adams1, Elsa I. Mangiarua1, Paulette S. Wehner3 and William D. McCumbee1
1 Departments of Physiology, 2 Pathology, and 3 Cardiovascular Services, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia

Address correspondence to William D. McCumbee, Ph.D., Dept of Physiology, Joan C. Edwards School of Medicine, Marshall University, 1542 Spring Valley Drive, Huntington, WV 25704-9340, USA; tel 304 696 7366; fax 304 696 7381; e-mail mccumbee{at}marshall.edu.

This study assessed the progression of renal damage in obese Zucker rats in response to deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Renal damage was evaluated by light microscopy and urine analysis at weekly intervals during the developmental phase of DOCA-salt hypertension and once during the plateau phase 42 days after the onset of treatment. Decreased tubular function was evident by day 8, as indicated by a significant increase in urine N-acetyl-ß-D-glucosaminidase activity and glucose excretion. The tubular index, a measure of tubular damage, was significantly elevated by day 15 and continued to increase throughout the experiment. Glomerular damage, which was evident by day 8, was followed by increased urine albumin excretion by day 15. Only a few sclerotic renal glomeruli were apparent before the plateau phase; however, by day 42, approximately 50% of the glomeruli were sclerotic. Hyperplastic vascular changes were mild at day 8 and slowly increased in severity during the developmental phase. By day 42 the vascular changes were severe with some vessels so hyperplastic that their lumens were almost occluded. These findings show progressive changes in renal structure and function that begin as early as day 8 and increase progressively until severe changes are present at day 42, resulting in an end-stage kidney.

Keywords: hypertension, obesity, renal tubular damage, deoxycorticosterone acetate, glomerulosclerosis






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