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

Access this Article

Author(s)

Abstract

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.

Journal

  • The Japanese Journal of Pharmacology

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

    The Japanese Pharmacological Society

References:  25

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008197625
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4948543
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top