Up-regulation of proteinase-activated receptor 1 and increased contractile responses to thrombin after subarachnoid haemorrhage.

摘要: Background and purpose: The mechanism for the development of post-haemorrhagic cerebral vasospasm after subarachnoid haemorrhage (SAH) still remains unknown. Experimental approach: We investigated role thrombin its receptor PAR1 in hyper-contractility basilar artery a rabbit double model, which received two injections autologous blood into cisterna magna. Key results: In isolated from control rabbits, thrombin, only at 10 units ml−1, induced transient endothelium-dependent relaxation slight smooth muscle contraction. In SAH, contractile response to was markedly enhanced, while relaxant effect remained unchanged. The enhancement responses also observed absence endothelium an enhanced contraction concentrations higher than 0.3 units ml−1. PAR1-activating peptide SAH. However, high K+ endothelin-1, myofilament Ca2+-sensitivity unchanged An immunoblot analysis suggested up-regulation artery. heparinization before injection prevented peptide. Conclusions implications: The present study demonstrated, first time, that Mechanistically, our findings activation following hemorrhage up-regulated expression PAR1, thereby inducing hyper-responsiveness thrombin. British Journal Pharmacology (2007) 152, 1131–1139; doi:10.1038/sj.bjp.0707435; published online 3 September 2007