Prevention of stroke and brain damage with calcium antagonists in animals

Abstract

In a rat model of embolic stroke (permanent occlu­sion of the left middle cerebral artery [MCAO]), various 1, 4-dihydropyridine calcium antagonists have been shown to attenuate brain damage and the resultant functional impairment when administered after MCAO. Dose-response curves reveal that isra-dipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When isra­dipine is used to normalize the high blood pressure in spontaneously hypertensive rats, it will, in addi­tion, also protect the brain from damage engen-dered by a subsequent stroke. This is not the case if blood pressure is controlled with a calcium antago­nist which does not cross the blood-brain barrier, suggesting that the brain protection seen with isra­dipine is not due to blood pressure normalization. Isradipine, when used as an antihypertensive, ap­pears to have an additional beneficial effect within the brain itself. As high blood pressure is a major risk factor for stroke, such an additional benefit with isradipine would be particularly valuable in antihypertensive therapy. Am J Hypertens 1991; 4:121S-127S. © 1991 by the American Journal of Hypertension, Ltd.