PROPHYLACTIC EFFECTS OF NOVEL DIHYDROPYRAZOLOPYRIDINE (83-0256) AND DIHYDROTHIENOPYRIDINE (83-0312, 83-0327) CALCIUM-ANTAGONISTS IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

The prophylactic effects of several Ca antagonists against the incidence of cerebral stroke in stroke‐prone spontaneously hypertensive rats (SHRSP) (9‐17 weeks of age) fed a stroke‐prone (SP) diet (Na, 0.39%) were investigated for 8 weeks. The control SHRSP administered 1% gum arabic solution showed 87.5% mortality due to cerebral stroke during the experimental period. Daily oral administration of nifedipine or dihydrothienopyridine derivatives (83‐0312, 83‐0327) at 3 mg/kg or of nicardipine or dihydropyrazolopyridine derivative (83‐0256) at 10 mg/kg markedly inhibited the incidence of cerebral stroke and decreased mortality in SHRSP. Also markedly inhibited were the early appearances of proteinuria and occult blood in the urine observed with control SHRSP. Potencies of prophylactic effects of Ca antagonists on the incidence of stroke decreased in the following order: 83‐0327 > nifedipine ≥ 83‐0312 ≥ 83‐0256 > nicardipine. These potencies corresponded well with those of the acute antihypertensive effects. The most potent prophylactic effect against stroke was observed following the administration of 83‐0327 and this effect was considered to be intimately related with its lasting antihypertensive effect. Copyright © 1990 Wiley‐Liss, Inc.