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.
Davy
M
M
Midol-Monnet
M
M
Heimburger
M
M
Wepierre
J
J
Cohen
Y
Y
D000070:Acebutolol / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011217:Practolol / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D000070:Acebutolol; D011802:Quinidine; D007545:Isoproterenol; D011217:Practolol