To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia1...To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia11y reported by various authors. We have performed investigations in anesthetized Sprague-Dawley rats- Intracisternal injection (i. c. ) of ET-l (10-11, 10-10, 10-9 mol/kg) could induce acute dose-dependent CVS, furthermore, the highest dose of ET-l (lO-’ mo1/kg) had a biphasic response in CVS of a 24-hour duration. However, the CVS by ET-1 (10-9 mol/kg) could be prevented effectively by previous i. c. of BQ-123 in a dose-dependent manner (10-9, 10-8, 10-7 mol/kg), of which the i. c- of BQ-123 (10-7mol/kg) could abolish the CVS completely. i. c. of BQ-123 (10-7 mol/kg) before SAH induced by a single i. c, of 150 pl autologous fresh blood directly to the Willis circle cou1d prevent the following CVS largely, which was a biphasic response and long-lasting (duration of 72 h). We conclude that subarachnoid application of ETA-receptor antagonist can effecti vely prevent CVS induced by ET-1 and SAH, and ET-1 may be the major mediator responsible for the CVS following SAH.展开更多
文摘To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia11y reported by various authors. We have performed investigations in anesthetized Sprague-Dawley rats- Intracisternal injection (i. c. ) of ET-l (10-11, 10-10, 10-9 mol/kg) could induce acute dose-dependent CVS, furthermore, the highest dose of ET-l (lO-’ mo1/kg) had a biphasic response in CVS of a 24-hour duration. However, the CVS by ET-1 (10-9 mol/kg) could be prevented effectively by previous i. c. of BQ-123 in a dose-dependent manner (10-9, 10-8, 10-7 mol/kg), of which the i. c- of BQ-123 (10-7mol/kg) could abolish the CVS completely. i. c. of BQ-123 (10-7 mol/kg) before SAH induced by a single i. c, of 150 pl autologous fresh blood directly to the Willis circle cou1d prevent the following CVS largely, which was a biphasic response and long-lasting (duration of 72 h). We conclude that subarachnoid application of ETA-receptor antagonist can effecti vely prevent CVS induced by ET-1 and SAH, and ET-1 may be the major mediator responsible for the CVS following SAH.
