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 inhibition of
nitric oxide (NO). Male Wistar rats were given distilled water (control),
NG-nitro-L-arginine methyl ester (
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 reduced 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 ventricular wall (83.3 +/- 3.0 v 69.8 +/- 1.8 mm2 in control).
Nephrosclerosis and myocardial interstitial
fibrosis were documented histologically. The plasma
renin activity was significantly higher in rats treated with
L-NAME than in the control rats. The concomitant administration of
imidapril (10 mg/L) with
L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 +/- 1.8 mm2), 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. Thus, the chronic inhibition of NO synthesis in rats produced
nephrosclerosis 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 reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of
calcium channels in preventing hypertensive tissue injury.