Volume 105, Issue 1 p. 103-106
Free Access

Endothelium-dependent relaxation of rabbit middle cerebral artery to a histamine H3-agonist is reduced by inhibitors of nitric oxide and prostacyclin synthesis

L. Ea Kim

Corresponding Author

L. Ea Kim

Laboratoire de Pharmacologie, UFR de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France

Laboratoire de Pharmacologie, UFR de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, FranceSearch for more papers by this author
J. Javellaud

J. Javellaud

Laboratoire de Pharmacologie, UFR de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France

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N. Oudart

N. Oudart

Laboratoire de Pharmacologie, UFR de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France

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First published: January 1992
Citations: 52

Abstract

  • 1

    The possible involvement of prostanoids and endothelium-derived relaxing factor (EDRF) in the vasodilatation induced by a histamine H3-agonist was examined in the rabbit perfused middle cerebral artery preconstricted with K+ (50 mm).

  • 2

    The endothelium-dependent relaxation to (R)-α-methylhistamine [(R)-α-MeHA] was competitively antagonized by thioperamide (an H3-antagonist) with a pA2 of 9.05, but unaffected by propranolol, atropine, l- and d-sulpiride. This effect was stereoselective since the (S)-isomer was 100 times less potent than the (R)-isomer.

  • 3

    Two inhibitors of nitric oxide synthesis, NG-nitro-l-arginine methyl ester (l-NAME) and NG-monomethyl-l-arginine (l-NMMA), inhibited the relaxation induced by (R)-α-methylhistamine. The inhibitory effects of 10−5 m NG-nitro-l-arginine methyl ester and 10−5 m NG-monomethyl-l-arginine were reversed by equimolar concentrations of l-arginine, but strongly enhanced by 10−4 m tranylcypromine. Tranylcypromine alone (10−5 m−10−4 m) partially reduced the (R)-α-methylhistamine-induced relaxation. Both dexamethasone and indomethacin also inhibited this relaxation.

  • 4

    The results suggest that the H3-mediated relaxation of the rabbit middle cerebral artery may involve release of both a prostanoid, probably prostacyclin, and endothelium-derived relaxing factor. The relaxant effects of these two endogenous compounds appear to be synergistic.