Manidipine attenuates a progressive renal injury in remnant kidneys of rats.
The effects of a calcium antagonist, manidipine, on the outcome of the remnant kidney model of chronic renal failure in rats were studied. After 5/6 nephrectomy (5/6 Nx), rats were assigned to one of the following groups, and fed: Nx without manidipine, group 1; diet with 0.01% manidipine, group 2. A sham 5/6 Nx group was also included as the control. Each diet contained the same calories (3.44 kcal/g) and protein (25% casein). Increased systolic blood pressure seen after 8 weeks postablation was less with manidipine in group 2. Group 2 also had significantly less proteinuria. By 12 weeks postablation, group 1 showed severe parenchymal damage, characteristic of end-stage renal pathology. These changes were prevented by manidipine. The percentage of glomeruli with severe structural damage including sclerosis and/or hyalinosis, arbitrarily defined as glomerular sclerosis index (GSI) was significantly less in group 2 (41 +/- 11%) compared with group 1 (58 +/- 10%). Tubulointerstitial injury (TII) was also less in group 2 (29.1 +/- 9.1%) compared with group 1 (45.1 +/- 10.3%). Sham-Nx control group without manidipine showed normal renal morphology (GSI, 0.2 +/- 0.6, TII, 3.8 +/- 1.0). These results indicate that manidipine attenuates the development of end-stage renal pathology in the remnant kidney model of chronic renal failure in rats. The mechanism(s) remains to be elucidated.
Kobayashi
S
S
First Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Hishida
A
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007676:Kidney Failure, Chronic / Q000517:prevention & control*; D008297:Male; D009392:Nephrectomy; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011916:Rats, Inbred F344
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine