Abstract
The present study investigated the development of hypertension and the functional and morphological changes in the kidney in Dahl salt-sensitive (Dahl S) rats fed with a normal salt diet during aging. Furthermore, the effects of calcium channel antagonists nitrendipine and nicardipine on these changes were examined. The rats showed proteinuria from 6 weeks of age and gradually developed hypertension accompanied by the decrease in the glomerular filtration rate during aging. Glomerular screlosis and degeneration of the renal tubule were found by histological examinations at 17 weeks of age. Nitrendipine (20 mg/kg chow), given from 7 weeks of age for 10 weeks, inhibited the elevation in systolic blood pressure from 3 weeks after the dosing, whereas nicardipine (20 mg/kg chow) inhibited it only at 5 weeks after dosing. Both drugs decreased glomerular sclerosis, but did not affect the glomerular filtration rate, urine volume, urinary excretion of protein and N-acetyl-β-D-glucosaminidase and serum concentrations of creatinine and urea nitrogen. These results demonstrated that Dahl S rats fed with a normal salt diet spontaneously developed the renal disorder in the early stage of hypertension and reinforce the validity of nitrendipine for the treatment of hypertensive patients with renal failure.
