Mibefradil prevents L-NAME-exacerbated nephrosclerosis in spontaneously hypertensive rats

Objective To determine the potential renal protective effects of a novel ca lcium channel blocker mibefradil in chronic renal failure. Method We compared the long-term effects of mibefradil with an angiotensin- converting enzyme inhibitor cilazapril on blood pressure, proteinuria, rena l function and histological alterations in N-nitro-L-arginine methylester ( L-NAME)-treated spontaneously hypertensive rats (SHR), Three groups of SHR were studied for 45 days: group 1 (n = 14), treated with L-NAME only (50 mg /l in the drinking water); group 2 (n = 15) L-NAME plus co-treatment with m ibefradil (30 mg/kg per day); group 3 (n =15), L-NAME plus co-treatment wit h cilazapril (10 mg/kg per day). Results Both mibefradil and cilazapril attenuated the increased systolic bl ood pressure, and prevented the development of proteinuria and the decrease d creatinine clearance (Ccr) seen at day 42 in the group treated with L-NAM E alone, Notably, mibefradil had similar effects to cilazapril on proteinur ia and Ccr, despite a reduced antihypertensive effect. All animals receivin g mibefradil cotreatment remained alive throughout the experiment, whereas the mortality rate was 43% in SHR treated with L-NAME alone. Both mibefradi l and cilazapril completely prevented renal structural damage as assessed b y scoring glomerular, tubulo-interstitial and vascular lesions. Conclusions Our data show that mibefradil prevented the development of hype rtension and proteinuria, renal functional impairment and nephrosclerosis, and also improved animal survival. The renal protective effects of mibefrad il were at least equivalent to those of an ACE inhibitor in this animal mod el of chronic renal failure. I Hypertens 1999, 17:1489-1495 (C) Lippincott Williams & Wilkins.