Long-term effect of manidipine on renal function and structure in uninephrectomized spontaneously hypertensive rats.
1. Long-term effects of manidipine hydrochloride (MAN), a calcium channel blocker, were examined in three groups of spontaneously hypertensive rats (SHR). Group 1 was given uninephrectomy (UNX) and MAN treatment, group 2 was given UNX and was not treated with MAN and group 3 was given neither UNX nor MAN treatment. 2. At week 15 after UNX, inulin clearance in group 1 rats decreased compared with rats in groups 2 and 3, but remained at the same level at week 40, when the level in group 2 rats declined below that in rats in groups 1 and 3. 3. Glomerular and tubulointerstitial lesions did not differ at week 15 after UNX among the three groups, whereas at week 40 both were advanced in the order of groups 2, 1 and 3. 4. Proteinuria did not differ between rats in groups 1 and 2 over the experimental period. 5. At week 15, the kidney weights of group 1 rats were greater than those of group 2 rats, indicating more prominent tubular hypertrophy in the former group. This was confirmed by morphometry of the proximal tubuli. In contrast, the glomerular volumes of rats in groups 1 and 2 were enlarged compared with that of rats in group 3, with no difference between the former two groups. 6. The findings suggest that MAN exerts renoprotective effects in SHR, both with regard to function and morphology. An effect on glomerular haemodynamics was considered to more likely be the mechanism underlying the renoprotective effect of MAN rather than that of a lowering of systemic blood pressure. 7. Augmented tubular hypertrophy after MAN treatment was an unexpected finding of the present study and the biological significance of this finding remains to be explored.
Fujimaki
M
M
First Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Nagase
M
M
Uchida
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000473:pathology / Q000503:physiopathology*; D007444:Inulin / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007672:Kidney Cortex / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008297:Male; D009578:Nitrobenzenes; D010879:Piperazines; D011507:Proteinuria; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine; D007444:Inulin