Calcium antagonists: effects on cerebral blood flow and blood‐brain barrier permeability in the rat

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Abstract
Because they affect isolated cerebral arteries, some calcium antagonists have been studied on the intact cerebral circulation of the rat. Global cerebral blood flow (133Xe clearance technique) was measured in anaesthetized rats. Neither perhexiline (0.1 μg/kg to 1.0 mg/kg, i.v.) nor diltiazem (0.06–0.6 mg/kg, i.v.) had any significant effect on resting cerebral blood flow when measured 5 min after each dose. A high dose of nifedipine (1.0 mg/kg, i.v.) was administered during induced hypocapnia. Nifedipine failed to modify the hypocapnic vasoconstriction of the cerebral vasculature when compared to vehicle‐treated rats. The possibility of discrete changes in regional cerebral blood flow was investigated. Local cerebral blood flow was measured in a number of brain regions by the [14C]‐ethanol technique 15 min after the administration of nifedipine (20 or 100 μg/kg, i.v.). Nifedipine had no apparent effect on regional blood flow in the rat brain. Acute arterial hypertension increases protein leakage into the brain, a phenomenon susceptible to drugs that act on endothelial pinocytosis which is known to be calcium‐dependent. The increase in protein extravasation, induced by the intravenous administration of either angiotensin II or adrenaline, was unchanged in rats previously treated with either nimodipine (20 μg/kg, i.v.) or nifedipine (50 μg/kg, i.v.) when dissolved in ethanol alone. However, nifedipine (20 μg/kg, i.v.) when dissolved in a solution of polyethylene glycol and ethanol further enhanced the hypertension‐induced increase in brain albumin permeability. In conclusion, we have been unable to demonstrate any apparent effects of various calcium antagonists on the intact cerebral circulation of the rat, despite the number of different experimental models used.