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

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The present study was designed to examine the role of basally released nitric oxide in relaxations to an ATP-sensitive K<SUP>+</SUP> 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<SUP>-7</SUP> to 10<SUP>-6</SUP> M), levcromakalim (10<SUP>-8</SUP> to 10<SUP>-5</SUP> M) or a nitric oxide donor, 1-hydroxy-2-oxo-3-(<I>N</I>-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7, 10<SUP>-9</SUP> to 10<SUP>-5</SUP> M), was added in a cumulative fashion. Relaxations to levcromakalim (10<SUP>-8</SUP> to 10<SUP>-5</SUP> 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 (<I>N<SUP>G</SUP></I>-nitro-L-arginine methyl ester, 10<SUP>-4</SUP> M) and soluble guanylate cyclase (1<I>H</I>-[1, 2, 4]oxadiazolo[4, 3-<I>a</I>]quinoxaline-1-one; ODQ, 10<SUP>-5</SUP> M) and a scavenger of nitric oxide (carboxy-PTIO, 10<SUP>-3</SUP> 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<SUP>+</SUP> channel inhibitor, glibenclamide (10<SUP>-5</SUP> M), abolished relaxations to levcromakalim in aortas with or without endothelium, whereas glibenclamide did not alter relaxations to NOC-7 (10<SUP>-9</SUP> to 10<SUP>-5</SUP> 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<SUP>+</SUP> channels, although these channels do not mediate relaxations to exogenously applied nitric oxide.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 81(4), 362-366, 1999-12-01

    The Japanese Pharmacological Society

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Cited by:  1


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