Effects of manidipine on blood pressure and renal function in salt-loaded, spontaneously hypertensive rats

The purpose of this study was to investigate the effects of 4-week oral administration of manidipine (40 mg daily), a newly developed calcium channel blocker, on blood pressure and renal function in salt-loaded (8% NaCl) spontaneously hypertensive rats. Systolic blood pressure of spontaneously hypertensive rats increased from 167 +/- 4 to 221 +/- 7 mmHg with salt loading for 4 weeks; manidipine completely prevented this elevation in blood pressure. Urinary excretion of sodium in salt-loaded spontaneously hypertensive rats was twelve-fold compared with those receiving a normal diet (0.38% NaCl). The pressure-natriuresis relationship was obtained during week 4 of the metabolic study. At similar renal perfusion pressures, sodium excretion was significantly higher in salt-loaded rats than in rats fed a normal diet. Glomerular filtration rate and renal plasma flow were similar between the two groups. In salt-loaded spontaneously hypertensive rats, treatment with manidipine improved the pressure-natriuresis relationship toward lower pressures. Further, manidipine attenuated the autoregulation of glomerular filtration rate and renal plasma flow. These results indicate that manidipine normalizes the relation between sodium excretion and renal perfusion pressure in salt-loaded spontaneously hypertensive rats by resetting pressure natriuresis.