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NEUROSURGICAL ANESTHESIOLOGY AND NEUROSCIENCE

The Role of 20-Hydroxyeicosatetraenoic Acid in Cerebral Arteriolar Constriction and the Inhibitory Effect of Propofol

Keiko Hama-Tomioka, MD^*, Hiroyuki Kinoshita, MD, PhD^*, Toshiharu Azma, MD, PhD, Katsutoshi Nakahata, MD, PhD^*, Naoyuki Matsuda, MD, PhD, Noboru Hatakeyama, MD, PhD, Hirosato Kikuchi, MD, PhD, and Yoshio Hatano, MD, PhD

From the *Department of Anesthesiology, Wakayama Medical University, Wakayama; Department of Anesthesiology, Saitama Medical University, Saitama; Department of Primary Care and Emergency Medicine, Graduate School of Medicine, Kyoto University, Kyoto; and Department of Anesthesiology, Toyama University School of Medicine, Toyama, Japan.

Address correspondence and reprint requests to Hiroyuki Kinoshita, MD, PhD, Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan. Address e-mail to hkinoshi{at}nike.eonet.ne.jp or hkinoshi{at}wakayama-med.ac.jp.

Abstract

BACKGROUND: We conducted this study to examine, in cerebral parenchymal arterioles, whether 20-hydroxyeicosatetraenoic acid (20-HETE) induces constrictor responses via superoxide and whether propofol reduces this constriction.

METHODS: Electrical field stimulation or 20-HETE was applied to rat brain slices monitored by computer-assisted microscopy. In some experiments, a Na⁺ channel antagonist tetrodotoxin, a 20-HETE synthesis inhibitor HET0016, a superoxide scavenger, Tiron, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium (DPI) and gp91ds-tat, or propofol was added. The superoxide level in the brain slice and the production rate in the absence of slices were evaluated by dihydroethidium fluorescence or cytochrome c reduction with a superoxide-generating system, respectively.

RESULTS: Electrical stimulation induced constriction of the cerebral parenchymal arteriole, whereas this response was abolished by tetrodotoxin, HET0016, Tiron, or DPI. 20-HETE (10^–8–10^–6 mol/L) produced arteriolar constriction, which was inhibited by Tiron or DPI. Propofol reduced the constriction induced by electrical stimulation or 20-HETE. 20-HETE induced superoxide production in the brain slice, which was reduced by Tiron, gp91ds-tat, or propofol. However, propofol did not alter the superoxide production rate in the absence of brain slices.

CONCLUSIONS: Either neuronal transmission-dependent or exogenous 20-HETE seems to induce cerebral parenchymal arteriolar constriction via superoxide production resulting from NADPH oxidase activation. Propofol is likely to prevent this constriction via inhibition of NADPH oxidase, but not by its scavenging effect on superoxide.