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Central action of beta-adrenoceptor antagonists on blood pressure after acute administration in rats.

The effect of an i.v. administration of some beta-adrenergic blocking drugs on blood pressure has been investigated in rats after blood-brain barrier (BBB) opening. Practolol and atenolol which do not penetrate the BBB, induced an immediate hypotensive effect after BBB breakdown by intracarotid (i.c.) injection of cetrimonium. In 39 week-old spontaneously hypertensive rats, practolol (15 mg/kg i.v.) and atenolol (3 mg/kg i.v.) induced a large drop in blood pressure while only a slight decrease was shown in normotensive ones. Likewise, acebutolol induced a significantly greater hypotension after BBB damage. On the other hand, the effects of dl-propranolol (5 mg/kg), quinidine (2.5 mg/kg) and isoproterenol (3 micrograms/kg) on blood pressure were not modified by pretreatment with cetrimonium i.c., while the hypotension induced by d-propranolol (5 mg/kg) was shortened. These results indicate that beta-adrenergic blocking agents with a low degree of lipophily can induce a hypotensive effect when their penetration into brain is largely enhanced after BBB opening either by prolonged hypertension or by cetrimonium. This effect is only dependent on their action on beta-adrenoreceptors; membrane stabilizing effect and intrinsic sympathomimetic activity do not seem to be involved.