Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.
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 > or = 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. These findings suggest that amlodipine and carvedilol, with their antioxidant properties and antihypertensive activity, would be useful to inhibit neuronal cell death in the treatment of cerebrovascular stroke and neurodegenerative diseases in hypertensive patients.
Yamagata
Kazuo
K
Laboratory of Nutritional Biochemistry and Center of Excellence Program in the 21st Century, School of Food and Nutritional Sciences, The University of Shizuoka, Shizuoka, Japan. yamagata@brs.nihon-u.ac.jp
Ichinose
Shizuko
S
Tagami
Motoki
M
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004176:Dipyridamole / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000473:pathology*; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000517:prevention & control; D020521:Stroke / Q000473:pathology / Q000517:prevention & control*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D002227:Carbazoles; D018696:Neuroprotective Agents; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D014810:Vitamin E; D017311:Amlodipine; D004176:Dipyridamole; D010100:Oxygen