ANTIHYPERTENSIVE AGENTS PREVENT NEPHROSCLEROSIS AND LEFT-VENTRICULAR HYPERTROPHY INDUCED IN RATS BY PROLONGED INHIBITION OF NITRIC-OXIDE SYNTHESIS

We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibit ion of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl eater (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly red uced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g in control), and the area of the left ve ntricular wall (83.3 +/- 3.0 v 69.8 +/- 1.8 mm(2) in control). Nephros clerosis and myocardial interstitial fibrosis were documented histolog ically. The plasma renin activity was significantly higher in rats tre ated with L-NAME than in the control rats. The concomitant administrat ion of imidapril (10 mg/L) with L-NAME completely normalized the tail- cuff pressure, the LVH (70.8 +/- 1.8 mm(2)), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced effects, but to a lesser extent. T hus, the chronic inhibition of NO synthesis in rats produced nephroscl erosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reductio n in NO production, implying that in rats the inhibition of the renin- angiotensin system is more effective than the blockade of calcium chan nels in preventing hypertensive tissue injury. (C) 1998 American Journ al of Hypertension, Ltd.