title: Subarachnoid hemorrhage induces enhanced expression of thromboxane A2 receptors in rat cerebral arteries.
abstract: Cerebral ischemia remains the key cause of morbidity and mortality after subarachnoid hemorrhage (SAH) with a pathogenesis that is still poorly understood. The aim of the present study was to examine the involvement of thromboxane A(2) receptors (TP) in the pathophysiology of cerebral ischemia after SAH in cerebral arteries. SAH was induced in rats by injecting 250 microl of blood into the prechiasmatic cistern. Two days after the SAH, cerebral arteries were harvested and contractile responses to the TP receptor agonist U46619 were investigated with myographs. In addition, the contractile responses were examined after pretreatment with selective TP receptor antagonist GR3219b. The TP receptor RNA and protein levels were analyzed by quantitative real-time PCR and immunohistochemistry, respectively. The global and regional cerebral blood flows (CBFs) were quantified with an autoradiographic technique. SAH resulted in enhanced contractile responses to U46619 as compared to sham. The TP receptor antagonist GR3219b abolished the enhanced contractile responses to U46619 observed after SAH. The TP receptor mRNA level was elevated after SAH as compared to sham. The level of TP receptor protein on the smooth muscle cells (SMCs) was increased in SAH compared to sham. Global and regional CBFs were reduced in SAH as compared to sham. The results demonstrate that SAH results in CBF reduction and this is associated with the enhanced expression of TP receptors in the SMC of cerebral arteries and microvessels.
authors.affiliation: Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Sweden. saema.ansar@med.lu.se
authors.forename: Saema
authors.initials: S
authors.lastname: Ansar
authors.forename: Carl
authors.initials: C
authors.lastname: Larsen
authors.forename: Aida
authors.initials: A
authors.lastname: Maddahi
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid