PREVENTIVE EFFECT OF IGANIDIPINE ON RENAL AND CEREBRAL INJURIES IN SALT-INDUCED HYPERTENSION

Iganidipine, a new water-soluble calcium antagonist, was administered at a nonhypotensive dose (NHD) of 0.3 mg/kg/day, a moderate-hypotensiv e dose (MHD) of 1.0 mg/kg/day, and a sustained-hypotensive dose (SHD) of 3.0 mg/kg/day to Dahl salt-sensitive (Dahl-S) rats fed a high-salt diet for 8 weeks. The effects on survival, and on renal and cerebral i njuries, were then examined. Iganidipine completely prevented hyperten sive death at the SHD and tended to increase the survival at the NHD a nd MHD. Iganidipine reduced glomerulosclerosis and renal arterial and tubular injuries in a dose-dependent manner. Iganidipine at the SHD, b ut not NHD or MHD, improved plasma creatinine, serum urea nitrogen, an d glomerular filtration rate. Iganidipine at all doses examined increa sed the urinary prostaglandin (PG) I-2 and PGE(2) but not PGF(2 alpha) or thromboxane B-2 and decreased plasma angiotensin II (All) level an d renin activity. The renal glomerular, tubular, and arterial injuries were significantly correlated with blood pressure (r = 0.56 to 0.80) and plasma AII level (r = 0.50 to 0.71) but not with urinary prostanoi ds. Iganidipine also reduced the incidence of cerebral infarction. The infarction area was slightly and significantly correlated with urinar y PGI, (r = 0.42) and PGE(2) (r = 0.41) but not with blood pressure or plasma AII. In conclusion, iganidipine prevented renal and cerebral i njuries in Dahl-S rats. In addition to the reduced blood pressure, the reduction of plasma AII and the increase of vasodilatory prostanoids may also partially contribute to the renal and cerebral protective eff ects of iganidipine. (C) 1997 American Journal of Hypertension, Ltd.