title: Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260.
abstract: The numerous situations which can result in cerebral hypoxic damage occur in newborn infants and in the elderly. In research aimed at more effective therapeutic intervention in ischaemic disorders of the brain, the animal model used and the principles of the causal therapy should be better outlined. The effects of the non-peptide AVPR (V2) antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation, and OPC-31260 treatment did not significantly reduce the hypoxic signs in the brain cortex; only a certain decrease in the pericapillary oedema was observed. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma AVP level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma AVP level was further enhanced by OPC-31260. These results demonstrate the important role of AVP in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal AVPR (V2). These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.
authors.affiliation: Institute of Physical Education and Sport Sciences, Faculty of Juhász Gyula Teacher Training College, University of Szeged, H-6725, Szeged, Topolya sor 2-4, Hungary.
authors.forename: Andor H
authors.initials: AH
authors.lastname: Molnár
authors.forename: Csaba
authors.initials: C
authors.lastname: Varga
authors.forename: Anikó
authors.initials: A
authors.lastname: Berkó
authors.forename: Imre
authors.initials: I
authors.lastname: Rojik
authors.forename: Arpád
authors.initials: A
authors.lastname: Párducz
authors.forename: Ferenc
authors.initials: F
authors.lastname: László
authors.forename: Ferenc A
authors.initials: FA
authors.lastname: László
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001929:Brain Edema / Q000517:prevention & control*; D002339:Carotid Arteries / Q000502:physiology; D004195:Disease Models, Animal; D004573:Electrolytes / Q000378:metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000187:drug effects; D015996:Survival Rate
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004573:Electrolytes; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C076251:mozavaptan