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ANESTHETIC PHARMACOLOGY

The Volatile Anesthetic Isoflurane Inhibits the Histamine-Induced Ca²⁺ Influx in Primary Human Endothelial Cells

Department of Anesthesiology, University of Würzburg, Würzburg, Germany

Address correspondence and reprint requests to Piet Tas, PhD, Klinik für Anaesthesiologie, Der Universität Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. Address e-mail to ptas{at}anaesthesie.uni-wuerzburg.de

Although isoflurane is a known vasodilator, the mechanism of isoflurane-induced vasodilation is not clear. One of the most important systems in this context is the nitric oxide (NO)-mediated vasodilation. The activity of this system is regulated by the agonist-induced Ca²⁺ influx rather than Ca²⁺ release from internal stores. A number of reports have studied the effect of volatile anesthetics on the cytoplasmic calcium concentration signaling in mammalian endothelial cells. However, similar studies using human endothelial cells are lacking. In this study, therefore, we investigated whether isoflurane affects the histamine-induced Ca²⁺ influx in primary cultures of human endothelial cells. Using confocal laser scanning microscopy and cells loaded with the Ca²⁺ indicator Fluo-3, we studied the effect of isoflurane on the plateau phase of the histamine-induced Ca²⁺ influx, which is considered to be due to capacitative Ca²⁺ entry. In addition, we measured the ion flux through capacitative Ca²⁺ channels directly by using Mn²⁺ ions, which, on entering the cell, quench the Fura-2 fluorescence. The results of these two methods were in close agreement and showed a dose-dependent inhibition of the capacitative Ca²⁺ entry by isoflurane. Isoflurane apparently depresses NO-mediated vasodilation when the observed inhibition is not compensated for downstream of the endothelial NO synthase activation.

IMPLICATIONS: In response to vasoactive agents, endothelial cells produce nitric oxide (NO), which relaxes the underlying smooth muscle cells. Inhaled anesthetics inhibit this system by an unknown mechanism. Using primary human endothelial cells, we showed that the anesthetic isoflurane depresses a Ca²⁺ influx, which is responsible for the activation of the endothelial NO synthase.

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				M.-O. Parat Could endothelial caveolae be the target of general anaesthetics? Br. J. Anaesth., May 1, 2006; 96(5): 547 - 550. [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999