Mechanisms involved in the relaxing effect of midazolam on coronary arteries.
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.
Klockgether-Radke
A P
AP
Georg-August University of Göttingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Göttingen, Germany. klockgether-radke@gmx.de
Pawlowski
P
P
Neumann
P
P
Hellige
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008874:Midazolam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D019335:Nitroarginine; D019789:Tetraethylammonium; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D015232:Dinoprostone; D008874:Midazolam; D005905:Glyburide; D007213:Indomethacin