EFFECTS OF MIDAZOLAM AND FLUMAZENIL ON CAROTID-SINUS BAROREFLEX CONTROL OF CIRCULATION IN RABBITS

We have studied the effects of midazolam and flumazenil on the carotid sinus baroreflex, by examining mean arterial pressure (MAP) and heart rate (HR) responses to partial or complete bilateral carotid occlusio n (BCO) in 12 conscious rabbits after aortic denervation. In eight rab bits, the responses to complete BCO were evaluated before and after cu mulative doses of midazolam 0.5 and 1.0 mg kg(-1), and after flumazeni l 0.3 mg kg(-1) following administration of midazolam. Midazolam and f lumazenil had no effect on MAP or HR before complete BCO and neither a ffected the MAP response to complete BCO. Midazolam 0.5 and 1.0 mg kg( -1) decreased the HR response to 60% and 58% of control, respectively. Flumazenil restored the midazolam-induced depression of the HR respon se to the control level. In the other four rabbits, we examined the MA P and HR responses to partial BCO (carotid artery pressure reduced by 5, 10 and 20 mm Hg) before and after midazolam 0.5 mg kg(-1) and after flumazenil 0.3 mg kg(-1) following administration of midazolam. The r esponse to partial occlusion showed the same tendency as the response to complete BCO. These results indicate that midazolam attenuated the HR response of the carotid sinus baroreflex, flumazenil restored this midazolam-induced depression and neither drug affected the MAP respons e.