Abstract
The influence of hypertension and of treatment with some dihydropyridine-type Ca2+ 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 Ca2+ 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.
Footnotes
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Send reprint requests to: Francesco Amenta, M.D., Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, via M. Scalzino 3, 62032 Camerino, Italy. E-mail:amenta{at}cambio.unicam.it
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↵1 This study was supported by a grant from Recordati Industria Chimica e Farmaceutica S.p.A., Milan, Italy.
- Abbreviations:
- SHR
- spontaneously hypertensive rats
- ACE
- angiotensin-converting enzyme
- WKY
- Wistar Kyoto
- PAS
- periodic acid-Schiff
- TIS
- tubular injury score
- GIS
- glomerular injury score
- Received January 26, 2000.
- Accepted May 17, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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