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

Br J Pharmacol. 1992 Jan;105(1):103-6. doi: 10.1111/j.1476-5381.1992.tb14218.x.


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)-alpha-methylhistamine [(R)-alpha-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)-alpha-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)-alpha-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.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Cerebral Arteries / drug effects
  • Dexamethasone / pharmacology
  • Endothelium, Vascular / drug effects*
  • Epoprostenol / biosynthesis*
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Methylhistamines / pharmacology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / metabolism*
  • Rabbits
  • Receptors, Histamine / drug effects*
  • Receptors, Histamine H3
  • Tranylcypromine / pharmacology
  • Vasodilator Agents / pharmacology*
  • omega-N-Methylarginine


  • Methylhistamines
  • Receptors, Histamine
  • Receptors, Histamine H3
  • Vasodilator Agents
  • omega-N-Methylarginine
  • Nitric Oxide
  • Tranylcypromine
  • alpha-methylhistamine
  • Dexamethasone
  • Arginine
  • Epoprostenol
  • NG-Nitroarginine Methyl Ester
  • Indomethacin