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Mechanisms involved in the relaxing effect of midazolam on coronary arteries

Published online by Cambridge University Press:  13 April 2005

A. P. Klockgether-Radke ,
P. Pawlowski ,
P. Neumann  and
G. Hellige
A. P. Klockgether-Radke
Affiliation:
Georg-August University of Göttingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Göttingen, Germany
P. Pawlowski
Affiliation:
Georg-August University of Göttingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Göttingen, Germany
P. Neumann
Affiliation:
Georg-August University of Göttingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Göttingen, Germany
G. Hellige
Affiliation:
Georg-August University of Göttingen, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Department of Anaesthesiological Research, Göttingen, Germany
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Abstract

Summary

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 F2α.

Results: Midazolam caused vasodilatation in a concentration-dependent manner. Relaxation was more pronounced in prostaglandin F2α precontracted segments than in those treated with potassium chloride (P < 0.001). Vasodilatation was unaffected by Nω-nitro-l-arginine, indomethacin and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BKCa K+ channel (a high conductance Ca2+-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 BKCa K+ channel, may contribute to the vasorelaxing effect of midazolam.

Keywords

ANAESTHETICS, INTRAVENOUS, midazolamARTERIES, coronary vesselsK+ CHANNELS, BKCa channel
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 2 , February 2005 , pp. 135 - 139
Copyright
2005 European Society of Anaesthesiology

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References

Jones DJ, Stehling LC, Zauder HL. Cardiovascular responses to diazepam and midazolam maleate in the dog. Anesthesiology 1979; 51: 430–434.Google Scholar
Reves JG, Kissin I, Fournier S. Negative inotropic effects of midazolam. Anesthesiology 1984; 60: 517–518.Google Scholar
Reves JG, Samuelson PN, Lewis S. Midazolam maleate induction in patients with ischaemic heart disease: haemodynamic observations. Can Anesth Soc J 1979; 26: 402–409.Google Scholar
Samuelson PN, Reves JG, Kouchoukos NT. Hemodynamic responses to anesthetic induction with midazolam or diazepam in patients with ischemic heart disease. Anesth Analg 1981; 60: 802–809.Google Scholar
Marty J, Gauzit R, Lefevre P. Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans. Anesth Analg 1986; 65: 113–119.Google Scholar
Chang KSK, Feng MD, Davis RG. Midazolam produces vasodilation by mixed endothelium-dependent and -independent mechanisms. Anesth Analg 1994; 78: 710–717.Google Scholar
Shiraishi Y, Ohashi M, Kanmura Y, Yamaguchi S, Yoshimura N, Itoh T. Possible mechanisms underlying the midazolam-induced relaxation of the noradrenaline-contraction in rabbit mesenteric resistance artery. Br J Pharmacol 1997; 121: 1155–1163.Google Scholar
Yamaguchi S, Kanmura Y, Yoshimura N. Effects of midazolam on contractions in smooth muscle of the rabbit mesenteric artery. Anesth Analg 1997; 84: 199–205.Google Scholar
Klockgether-Radke AP, Thudium A, Frerichs A, Kettler D, Hellige G. High-dose midazolam attenuates the contractile response to vasoconstrictors in coronary artery segments. Eur J Anaesthesiol 2003; 20: 289–293.Google Scholar
Hong SJ, Damron DS, Murray PA. Benzodiazepines differentially inhibit phenylephrine-induced calcium oscillations in pulmonary artery smooth muscle cells. Anesthesiology 1998; 88: 792–799.Google Scholar
Grupp IL, French JF, Matlib MA. Benzodiazepine Ro 5-4864 increases coronary flow. Eur J Pharmacol 1987; 143: 143–147.Google Scholar
Nilsson A, Tamsen A, Persson P. Midazolam–fentanyl anesthesia for major surgery. Plasma levels of midazolam during prolonged total intravenous anaesthesia. Acta Anaesthesiol Scand 1986; 30: 66–69.Google Scholar
Lauven PM, Stoeckel H, Schwilden H. Ein pharmakokinetisch begründetes Infusionsmodell für Midazolam. Anaesthesist 1982; 31: 15–20.Google Scholar
Moschitto LJ, Greenblatt DJ. Concentration-dependent plasma protein binding of benzodiazepines. J Pharm Pharmacol 1983; 35: 179–180.Google Scholar
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288: 373–376.Google Scholar
Moncada S, Vane JR. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A 2, and prostacyclin. Pharmacol Rev 1978; 30: 293–320.Google Scholar
Chen G, Suzuki H, Weston AH. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol 1988; 95: 1165–1174.Google Scholar
Palmer RMF, Ferrige AG, Moncada S. Nitric oxide accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 525–526.Google Scholar
Nagao T, Vanhoutte PM. Hyperpolarization as a mechanism for endothelium-dependent relaxation in the porcine coronary artery. J Physiol 1992; 445: 355–367.Google Scholar
Carlen PL, Gurevich N, Polc P. Low-dose benzodiazepine neuronal inhibition: enhanced Ca2+-mediated K+ conductance. Brain Res 1983; 271: 358–364.Google Scholar
Jacob MK, White RE. Diazepam, gamma-aminobutyric acid, and progesterone open K+ channels in myocytes from coronary arteries. Eur J Pharmacol 2000; 403: 209–219.Google Scholar