Hiroyuki Kinoshita1, Shizue Iwahashi2, Tetsuya
Kakutani2, Kazuhiro Mizumoto2,
Hiroshi Iranami2 and Yoshio Hatano2
1Department of Anesthesia, Japanese Red Cross Society Wakayama Medical Center, Wakayama 640 - 8269, Japan
2Department of Anesthesiology, Wakayama Medical Collage, Wakayama 641 - 0012, Japan
Abstract: The present study was designed to examine the role of basally released nitric oxide in relaxations to an ATP-sensitive K+ channel opener. Whether relaxations to levcromakalim are modulated by
endothelial removal or the inhibitors of vasodilator effects of endothelium-derived nitric oxide, were investigated in the rat aorta. During contractions to phenylephrine (3~10-7 to 10-6 M), levcromakalim (10-8 to 10-5 M) or a nitric oxide donor, 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7, 10-9 to 10-5 M), was added in a cumulative fashion. Relaxations to levcromakalim (10-8 to 10-5 M) were significantly reduced by the endothelium-removal. In aortas with endothelium, relaxations in response to levcromakalim were decreased by selective inhibitors of nitric oxide synthase (NG-nitro-l-arginine methyl ester, 10-4 M) and soluble guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one; ODQ, 10-5 M) and a scavenger of nitric oxide (carboxy-PTIO, 10-3 M). Relaxations to levcromakalim in aortas treated with these inhibitors are comparable to those seen in aortas without endothelium. KCl (30 mM) and an ATP-sensitive K+ channel inhibitor, glibenclamide (10-5 M), abolished relaxations to levcromakalim in aortas with or without endothelium, whereas glibenclamide did not alter relaxations to NOC-7 (10-9 to 10-5 M) in aortas without endothelium. These results suggest that in rat aortas, inhibition of vasodilator effects of basally released nitric oxide can reduce relaxations via ATP-sensitive K+ channels, although these channels do not mediate relaxations to exogenously applied nitric oxide.
Keywords: Aorta, ATP-sensitive K+ channel, Endothelium, Glibenclamide, Nitric oxide