title: Expression of vascular endothelial growth factor (VEGF) in rat brain after subarachnoid haemorrhage and endothelin receptor blockage with BQ-123.
abstract: Cerebral vasospasm is one of the most severe complications of subarachnoid haemorrhage (SAH), leading to pathological changes in the vessel wall itself and in the nervous tissue, due to ischaemia of endothelial cells and neurones. Amongst the known substances inducing vasospasm, the most potent spasmogenic effect is exerted by endothelin-1 (ET1). The constriction of cerebral arteries and obliteration of capillaries highly stimulates the secretion of growth factors by endothelial cells and induces compensatory formation of collateral circulation in response to brain ischaemia. Expression of vascular endothelial growth factor (VEGF), the main factor responsible for angiogenesis and vascular permeability, was found to be increased in hypoxic cells (irrespective of the cause of hypoxia) as well as in neoplastic cells in the brain. The aim of the study was to determine whether chronic vasospasm and hypoxia of endothelial cells stimulate expression of VEGF, and whether blockage of the endothelin receptor ET(A) reduces this expression. The SAH was induced experimentally in male Wistar rats and the ET(A) receptor antagonist--BQ-123 was administered into the cisterna magna. After 48 hours the brain was removed and expression of VEGF studied immunohistochemically on paraffin sections. We found that hypoxia of endothelial cells, induced by chronic vasospasm after SAH, caused increased expression of VEGF in brain vessels and neurones of the cerebral hemispheres, brain stem and cerebellum. After administration of the endothelin receptor antagonist BQ-123, no changes in VEGF expression in the brain were found.
authors.affiliation: Department of Physiology, Silesian University School of Medicine, Zabrze, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jośko
authors.forename: B
authors.initials: B
authors.lastname: Gwóźdź
authors.forename: S
authors.initials: S
authors.lastname: Hendryk
authors.forename: H
authors.initials: H
authors.lastname: Jedrzejowska-Szypułka
authors.forename: J
authors.initials: J
authors.lastname: Słowiński
authors.forename: J
authors.initials: J
authors.lastname: Jochem
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D001933:Brain Stem / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D002831:Choroid Plexus / Q000737:chemistry / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D065128:Endothelin Receptor Antagonists; D004805:Ependyma / Q000737:chemistry / Q000378:metabolism; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000959:Antihypertensive Agents; D016228:Endothelial Growth Factors; D065128:Endothelin Receptor Antagonists; D008222:Lymphokines; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C072247:cyclo(Trp-Asp-Pro-Val-Leu)