This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Kinoshita, H. Articles by Hatano, Y. Search for Related Content PubMed PubMed Citation Articles by Kinoshita, H. Articles by Hatano, Y. Related Collections Cardiovascular Mechanisms

---

CARDIOVASCULAR ANESTHESIA

The Role of K⁺ Channels in Vasorelaxation Induced by Hypoxia and the Modulator Effects of Lidocaine in the Rat Carotid Artery

Hiroyuki Kinoshita, MD PhD^*, Yoshiki Kimoto, MD, Katsutoshi Nakahata, MD^*, Hiroshi Iranami, MD^*, Mayuko Dojo, MD, and Yoshio Hatano, MD, PhD

*Department of Anesthesia, Japanese Red Cross Society, Wakayama Medical Center, and Department of Anesthesiology, Wakayama Medical University, Japan

Address correspondence and reprint requests to Hiroyuki Kinoshita, MD, PhD, Department of Anesthesia, Japanese Red Cross Society, Wakayama Medical Center, 4-20 Komatsubara-dori, Wakayama, Wakayama 640-8269, Japan. Address e-mail to hkinoshi{at}pd5.so-net.ne.jp

Hypoxia induces vasodilation, partly via the activation of K⁺ channels. Lidocaine impairs vasorelaxation mediated by a K⁺ channel opener, suggesting that this antiarrhythmic drug may inhibit hypoxia-induced vasodilation mediated by K⁺ channels. We designed the current study to determine whether, in the carotid artery, K⁺ channels contribute to vasorelaxation in response to hypoxia and whether lidocaine modulates vasorelaxation induced by K⁺ channels via pathophysiological and pharmacological stimuli. Rings of rat common carotid artery without endothelium were suspended for isometric force recording. During contraction to phenylephrine, hypoxia-induced vasorelaxation or concentration-response to an adenosine triphosphate-sensitive K⁺ channel opener was obtained changing control gas to hypoxic gas and the cumulative addition of levcromakalim, respectively. Hypoxia-induced vasorelaxation was significantly reduced by glibenclamide (5 µM) but not by iberiotoxin (0.1 µM), apamin (0.1 µM), BaCl₂ (10 µM), or 4-aminopyridine (1 mM). Levcromakalim-induced vasorelaxation was completely abolished by glibenclamide. Lidocaine (10–100 µM) concentration-dependently inhibited this vasodilation, whereas it did not affect hypoxia-induced vasodilation. These results suggest that adenosine triphosphate-sensitive K⁺ channels play a role in hypoxia-induced vasodilation in the rat carotid artery and that lidocaine differentially modulates vasodilation via these channels activated by pathophysiological and pharmacological stimuli.

IMPLICATIONS: In rat carotid artery, levcromakalim produced vasorelaxation mediated by adenosine triphosphate (ATP)-sensitive K⁺ channels, whereas hypoxia induced it partly via these channels. Lidocaine inhibited vasorelaxation induced by an ATP-sensitive K⁺ channel opener but not by hypoxia, indicating the differential mechanisms of modulatory effects of this antiarrhythmic drug on vasodilation via ATP-sensitive K⁺ channels activated by pathophysiological and pharmacological stimuli.