Effects of midazolam and flumazenil on carotid sinus baroreflex control of circulation in rabbits

Abstract

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 occlusion (BCO) in 12 conscious rabbits after aortic denervation. In eight rabbits, the responses to complete BCO were evaluated before and after cumulative doses of midazolam 0.5 and 1.0 mg kg-1, and after flumazenil 0.3 mg kg-1 following administration of midazolam. Midazolam and flumazenil had no effect on MAP or HR before complete BCO and neither affected 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 response to the control level. In the other four rabbits, we examined the MAP 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 response 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 response.