Amlodipine and Carvedilol Prevent Cytotoxicity in Cortical Neurons Isolated from Stroke-Prone Spontaneously Hypertensive Rats

Abstract

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-

Amlodipine-Induced Reduction of Oxidative Stress in the Brain Is Associated with Sympatho-Inhibitory Effects in Stroke-Prone Spontaneously Hypertensive Rats

“…In addition, amlodipine has been demonstrated to have anti-atherosclerotic and anti-inflammatory effects in animals (6-9) and humans (10). The mechanisms involved are complex, and include an increase in nitric oxide production (11) and a decrease in oxidative stress (12)(13)(14).…”

Protective Effect of Antioxidant Ebselen (PZ51) on the Cerebral Cortex of Stroke-Prone Spontaneously Hypertensive Rats

“…In an in vitro model system, antioxidants were the most important agents for the reduction of oxygen-free radical damage in cortical neurons of SHRsp (36). In our study, although there were no differences in blood pressure or BWR between the control and PZ51 group, electronic microscopy showed that the injury to neurons was alleviated by PZ51 administration.…”

Ischemic Neurodegeneration in Stroke-Prone Spontaneously Hypertensive Rats and Its Prevention with Antioxidants Such as Polyphenols

“…Furthermore, we have shown that ebselen, a seleno-organic antioxidant (Yamagata et al, 2008), amlodipine, and carvedilol (Yamagata et al, 2004) prevented neuronal cell death in SHRSP/Izm rats. Another study demonstrated that the expression of VCAM1 by TNF- in astrocytes isolated from SHRSP/Izm rats was increased compared with that in those from WKY/Izm rats.…”