A P Klockgether-Radke1, P Pawlowski, P Neumann, G Hellige. 1. Georg-August University of Göttingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Göttingen, Germany. klockgether-radke@gmx.de
Abstract
BACKGROUND AND OBJECTIVE: Hypotension, especially in elderly and hypovolaemic patients, is frequently associated with intravenous midazolam administration. The mechanisms are not completely understood. This study was designed to investigate the mechanisms involved in the relaxing effect of midazolam on coronary arteries. METHODS: The substance was studied in isolated porcine coronary artery rings precontracted by either potassium chloride or prostaglandin F2alpha. RESULTS: Midazolam caused vasodilatation in a concentration-dependent manner. Relaxation was more pronounced in prostaglandin F2alpha precontracted segments than in those treated with potassium chloride (P < 0.001). Vasodilatation was unaffected by Nomega-nitro-L-arginine, indomethacin and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BK(Ca) K+ channel (a high conductance Ca(2+)-sensitive K+ channel), dose dependently attenuated the vasodilating effect of midazolam (P < 0.01). CONCLUSIONS: Hyperpolarization of the smooth muscle cell in the vessel wall, elicited by the activation the BK(Ca) K+ channel, may contribute to the vasorelaxing effect of midazolam.
BACKGROUND AND OBJECTIVE:Hypotension, especially in elderly and hypovolaemic patients, is frequently associated with intravenous midazolam administration. The mechanisms are not completely understood. This study was designed to investigate the mechanisms involved in the relaxing effect of midazolam on coronary arteries. METHODS: The substance was studied in isolated porcine coronary artery rings precontracted by either potassium chloride or prostaglandin F2alpha. RESULTS:Midazolam caused vasodilatation in a concentration-dependent manner. Relaxation was more pronounced in prostaglandin F2alpha precontracted segments than in those treated with potassium chloride (P < 0.001). Vasodilatation was unaffected by Nomega-nitro-L-arginine, indomethacin and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BK(Ca) K+ channel (a high conductance Ca(2+)-sensitive K+ channel), dose dependently attenuated the vasodilating effect of midazolam (P < 0.01). CONCLUSIONS: Hyperpolarization of the smooth muscle cell in the vessel wall, elicited by the activation the BK(Ca) K+ channel, may contribute to the vasorelaxing effect of midazolam.