A new procedure for studying central acting cardiovascular drugs: the permeabilization of the blood-brain barrier.
There are substances with central cardiovascular action which do not reach the brain when given systemically, because they are unable to cross the blood-brain barrier in sufficient amount. We adapted an osmotic brain barrier disruption procedure in order to study the central cardiovascular effects of these substances. By studying the central hypotensive action of baclofen in the rat, we validated this technique with permeabilization of the brain area supplied by the carotid artery. In the cat, we permeabilized the area supplied by the vertebral artery, i.e. the medulla oblongata. Taurine, completely inactive when systemically or intravertebrally injected, became hypotensive after disruption with a hyperosmolar solution of mannitol. In conclusion, drugs inactive before permeabilization and becoming active after treatment with mannitol, could be considered as models for structural analogues with sufficient lipophily, permitting the crossing of the blood-brain barrier and, therefore, constituting models for new central hypotensive agents.
Feldman
J
J
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, UA 589 CNRS, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Bousquet
P
P
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002415:Cats; D005260:Female; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013654:Taurine / Q000008:administration & dosage / Q000494:pharmacology; D014711:Vertebral Artery
D002317:Cardiovascular Agents; D013654:Taurine; D001418:Baclofen