Nephroprotective effect of treatment with calcium channel blockers in spontaneously hypertensive rats.
The influence of hypertension and of treatment with some dihydropyridine-type Ca(2+) channel blockers and with the nondihydropyridine-type vasodilator hydralazine on the morphology of kidney was investigated in 26-week-old spontaneously hypertensive rats (SHR) and in age-matched Wistar-Kyoto rats. Fourteen-week-old SHR were treated for 12 weeks with a nonhypotensive dose of lercanidipine or with equihypotensive doses of lercanidipine, manidipine, nicardipine, and hydralazine. In control SHR, systolic pressure values were significantly higher in comparison with Wistar-Kyoto rats. Treatment with the low dose of lercanidipine did not reduce systolic blood pressure in SHR, whereas the higher dose of lercanidipine or other compounds tested significantly decreased systolic pressure values. Glomerular hypertrophy accompanied by signs of glomerulosclerosis, increase of mesangial cells, and convoluted tubules degeneration were observed in control SHR. Hypotensive doses of Ca(2+) antagonists countered glomerular injury, the increase of mesangial cells, the reduction of capsular space, and tubular degeneration. Hydralazine, in spite of its hypotensive activity, displayed a slight nephroprotective action. The nonhypotensive dose of lercanidipine countered in part glomerular injury, narrowing of capsular space, and tubular degeneration, and decreased mesangial cell augmentation in SHR. These results suggest that treatment with dihydropyridine-type Ca(+2) antagonists counters hypertensive glomerular and tubular changes occurring in SHR. The demonstration of nephroprotection by the nonhypotensive dose of lercanidipine suggests that the renal effects of the compound may be in part unrelated to its hemodynamic activity.
Sabbatini
M
M
Sezione di Anatomia Umana, Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università of Camerino, Italy.
Vitaioli
L
L
Baldoni
E
E
Amenta
F
F
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D014665:Vasodilator Agents; D006830:Hydralazine; C054218:manidipine; D009529:Nicardipine; C060343:lercanidipine