We previously reported that vitamin E prevents apoptosis in neurons during cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats (SHRSP). In this paper, we analyzed the effects of antihypertensives as well as vitamin E, which were added to neuron cultures after reoxygenation (20% O2) following hypoxia (1% O2). When added after hypoxia before reoxygenation, vitamin E conferred significant protection to neuronal cells. It was also shown that vitamin E conferred complete protection from neural cell death when added hypoxia and again before reoxygenation. At higher concentrations of vitamin E, strong neuroprotection was observed. Moreover, we verified that pretreatment with either amlodipine, carvedilol or dipyridamole consistently prevented cell death during hypoxia and reoxygenation (H/R). On the other hand, nilvadipine, a dihydropyridine-type calcium entry blocker, had no apparent effect on neuroprotection during H/R. The order of neuroprotective potency was vitamin E dipyridamole carvedilol amlodipine nilvadipine. In parallel experiments, we examined whether these antihypertensive agents were more effective when combined with vitamin E and dipyridamole. The results suggested that in our in vitro model system, antioxidants were the most important agents for the reduction of oxygen-free radical damage in cortical neurons. though pretreatments using vitamin E reduced this number (3,4). Furthermore, showed that vitamin E conferred similar protection against hypertension and cerebral thrombogenesis in SHRSP (5). SHRSP produce more greater concentrations of hydroxyl radicals than Wistar Kyoto rats (WKY) and thus are highly susceptible to neuronal damage (6). It is therefore possible that antioxidants effectively capture hydroxyl radicals produced during hypoxia and reperfusion, thereby preventing neuronal damage in SHRSP. Horakova et al. (7) substantiated the hypothesis that oxygen-free radical are involved in reoxygenation injury in hippocampal. They confirmed that lipid peroxidation was induced and that antioxi-