Effects of Etomidate and Midazolam on the Isolated Rabbit Abdominal Aorta and Pulmonary Artery

Yeom, Jong Hoon; Suh, Jung Kook; Yoo, Hee Koo

Abstract

Etomidate and midazolam are newly developed and used in clinical trials. Etmoidate, a carboxylated imidazole derivative, decreases systemic vascular resistance and increases the pulmonary artery pressure in vivo. Midazolam, a water soluble derivative of benzodiazepine, decreases pulmonary artery pressure and is useful for pulmonary hypertensive patients. This study was designed to investigate the direet effects of etomidate and midazolam on vascular tension of the rabbit abdominal aorta and the pulmonary artery in vitro. In the vascular preparations with or without endothelium, changes in tension were measured following cumulative administration of etomidate (10(-6)M, 10(-5) M, 5X10(-4) M) and midazolam (10(-6)M, 10(-5)M, 10(-4)M). Vascular effects of these drugs were also studied in the preparations pretreated with indomethacin, nitro(w)-L-arginine methyl ester (L-NAME) and methylene blue. The results wer as follows; 1) Etomidate and midazolam induced vasorelaxation and the degree of relaxation depended on the concentration. 2) After denudation of the endothelium, vasorelaxant effect of etomidate and midazolam was efficiently decreased in abdominal aorta but not in pulmonary artery. 3) Indomethacin reduced vasorelaxing effect of etomidate efficiently, but didn't affect vasorelaxing effect of midazolam. 4) Following pretreatment of vascular preparations respectively with L-NAME and methylene blue, the relaxing responses to etomidate (10(-5) and 5X10(-5) M) of both abdominal aorta and pulmonary artery were depressed. Also, depressed was the relaxing response of abdominal aorta to midazolam (10(-5) M). The results of present study suggest that etomidate and midazolam possess vasorelaxing effects in both rabbit aMominal aorta and pulmonary artery. The vascular effect of etomidate is mediated via the nitric oxide pathway and also in part, by PGI2, whereas part of the vascular effect of midazolam is associated with the nitric oxide pathway.