title: Antihypertensive agents prevent nephrosclerosis and left ventricular hypertrophy induced in rats by prolonged inhibition of nitric oxide synthesis.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Akuzawa
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Kurashina
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: J
authors.initials: J
authors.lastname: Hoshino
authors.forename: H
authors.initials: H
authors.lastname: Sakamoto
authors.forename: H
authors.initials: H
authors.lastname: Sumino
authors.forename: Z
authors.initials: Z
authors.lastname: Ono
authors.forename: R
authors.initials: R
authors.lastname: Nagai
mesh_terms: D017311:Amlodipine / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control*; D007093:Imidazoles / Q000008:administration & dosage*; D048289:Imidazolidines; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects*; D009400:Nephrosclerosis / Q000209:etiology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D017311:Amlodipine; D009569:Nitric Oxide; C065166:imidapril; D019331:NG-Nitroarginine Methyl Ester