High-dose midazolam and the attenuation of the contractile response to vasoconstrictors in coronary artery segments

Background and objective: Benzodiazepines may cause hypotension and are reported to interfere with smooth vascular muscle activity. The aim was to elucidate the influence of three different benzodiazepines on the vascular reactivity of coronary arteries. Methods: Using the model of isolated vessels, we studied the impact of midazolam (0.15, 1.5, 15 mug mL(-1)), diazepam (0.1, 1.0, 10 mug mL(-1)) and flunitrazepam (0.01, 0.1, 1.0 mug mL(-1)) on the contractile responses to histamine (2 x 10(-5) mol L-1) and serotonin (3 x 10(-5) mol L-1) in isolated intact and denuded coronary arteries. Results: Midazolam significantly attenuated the contractile response when administered in high concentrations (15 mug mL(-1)). This effect was more pronounced in intact than in denuded preparations (histamine: -22.7 versus -7.3%, P = 0.0079; serotonin: -47.1 versus -15.9%, P < 0.0001). Diazepam and flunitrazepam exerted no significant effects on the vascular tone of coronary arteries. Conclusions: Midazolam, but not diazepam or flunitrazepam, attenuates the contractile responses to vasoconstrictors in concentrations beyond those used in clinical practice. This effect is in part mediated by endothelial factors.