Jpn. J. Pharmacol. 81 (4), 362 - 366 (1999)


The Role of Endothelium-Derived Nitric Oxide in Relaxations
to Levcromakalim in the Rat Aorta

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


CopyrightŠ The Japanese Pharmacological Society 1999

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