Inhibitory effect of vasopressin receptor antagonist OPC-31260 on experimental brain oedema induced by global cerebral ischaemia.
The effects of the non-peptide vasopressin V(2) receptor 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 6 h 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. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma vasopressin level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma vasopressin level was further enhanced by OPC-31260. These results demonstrate the important role of vasopressin 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 vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.
Molnár
A H
AH
Department of Comparative Physiology, University of Szeged, Szeged, Hungary.
Varga
C
C
Berkó
A
A
Rojik
I
I
Párducz
A
A
László
F
F
László
F A
FA
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology* / Q000627:therapeutic use; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome; D014667:Vasopressins / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D017483:Receptors, Vasopressin; D014667:Vasopressins; C076251:mozavaptan; D012964:Sodium