Nephroprotective effect of treatment with calcium channel blockers in spontaneously hypertensive rats

The influence of hypertension and of treatment with some dihydropyridine-ty pe Ca2+ channel blockers and with the nondihydropyridine-type vasodilator h ydralazine on the morphology of kidney was investigated in 26-week-old spon taneously hypertensive rats (SHR) and in age-matched Wistar-Kyoto rats. Fou rteen-week-old SHR were treated for 12 weeks with a nonhypotensive dose of lercanidipine or with equihypotensive doses of lercanidipine, manidipine, n icardipine, and hydralazine. In control SHR, systolic pressure values were significantly higher in comparison with Wistar-Kyoto rats. Treatment with t he low dose of lercanidipine did not reduce systolic blood pressure in SHR, whereas the higher dose of lercanidipine or other compounds tested signifi cantly decreased systolic pressure values. Glomerular hypertrophy accompani ed by signs of glomerulosclerosis, increase of mesangial cells, and convolu ted tubules degeneration were observed in control SHR. Hypotensive doses of Ca2+ antagonists countered glomerular injury, the increase of mesangial ce lls, 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 glomeru lar injury, narrowing of capsular space, and tubular degeneration, and decr eased mesangial cell augmentation in SHR. These results suggest that treatm ent with dihydropyridine-type Ca+2 antagonists counters hypertensive glomer ular and tubular changes occurring in SHR. The demonstration of nephroprote ction by the nonhypotensive dose of lercanidipine suggests that the renal e ffects of the compound may be in part unrelated to its hemodynamic activity .