Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension

Abstract

The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178±4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n=8), enalapril-treated (n=8), or nitrendipine-treated (n=10). Sham-operated rats served as normotensive controls (128±3 mm Hg, n=8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment In contrast, in the nitrendipine-treated group albuminuria increased from 12.8±2 progressively to 163±55 compared with 19.2±9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38±0.1 versus 0.13±0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9±0.17 10-3 mm2) but lower in the enalapril-treated group (11.5±0.15 10-1 mm2) compared with the hypertensive controls (12.1±0.17 10-3 mm2). These data demonstrate that treatment with the calcium channel blocker nitrendipine is associated with progressive rise of albuminuria, glomerular size, and sclerosis in rats with two-kidney, one clip hypertension. Angiotensin converting enzyme inhibitors may retard the progression of glomerulosclerosis in the long term by its effects on blood pressure and glomerular size.