Subarachnoid hemorrhage induces enhanced expression of thromboxane A2 receptors in rat cerebral arteries

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 mu l of blood into the prechiasmatic cistem. 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. (C) 2009 Elsevier B.V. All rights reserved.