Hiroyuki Kinoshita1,*, Tetsuya Kakutani2, Hiroshi
Iranami1 and Yoshio Hatano2
1Department of Anesthesia, Japanese Red Cross Society Wakayama
Medical Center, 4-20 Komatsubara-dori, Wakayama 640-8269, Japan
2Department of Anesthesiology, Wakayama Medical Collage, Wakayama
641-0012, Japan
*Corresponding author. FAX: +81-73-426-1168
E-mail: hkinoshi@pd5.so-net.ne.jp
Abstract: Hydrogen peroxide and peroxynitrite induce relaxations
via ATP-sensitive K+ channels, indicating that oxygen-derived
free radicals may activate these channels. Levels of free radicals are increased
throughout the arterial wall in animal models of atherosclerosis, and therefore,
vasorelaxation via ATP-sensitive K+ channels may be augmented
in chronic hypertension. The present study was designed to determine whether
relaxations to an ATP-sensitive K+ channel opener, levcromakalim,
are increased in the aorta from spontaneously hypertensive rats (SHR) and
whether free radical scavengers reduce these relaxations. Rings of aortas
without endothelium taken from age-matched Wistar-Kyoto rats (WKY) and SHR
were suspended for isometric force recording. Relaxations to levcromakalim
(10-8 to 10-5
M), which are abolished by glibenclamide (10-5
M), were augmented in the aorta from SHR, compared to those in the aorta
from WKY. In the aorta from SHR, catalase (1200 U/ml), but neither superoxide
dismutase (150 U/ml) nor deferoxamine (10-4
M), reduced relaxations to levcromakalim, whereas in the aorta from WKY,
the free radical scavengers did not affect these relaxations. These results
suggest that in chronic hypertension, vasorelaxation to an ATP-sensitive
K+ channel opener is augmented and that hydrogen peroxide produced
in smooth muscle cells may partly contribute to these relaxations.
Keywords: ATP-sensitive K+channel, Catalase, Glibenclamide,
Hydrogen peroxide
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