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. 1996 Feb;5(1):69–74. doi: 10.1155/S0962935196000129

Endothelium-dependent relaxation of rat aorta to a histamine H3 agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na+,K+-ATPase

D M Djuric 1,✉, M T Nesic 1, I Z Andjelkovic 1
PMCID: PMC2365771  PMID: 18475701

Abstract

The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, β-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na+,K+-ATPase) was evaluated in a histamine H3 receptor agonist-induced ((R)α-methylhistamine, (R)α-MeHA) endothelium-dependent rat aorta relaxation assay. (R)α-MeHA (0.1 nM – 0.01 mM) relaxed endothelium-dependent rat aorta, with a pD2 value of 8.22 ± 0.06, compared with a pD2 value of 7.98 ± 0.02 caused by histamine (50% and 70% relaxation, respectively). The effect of (R)α-MeHA (0.1 nM – 0.01 mM) was competitively antagonized by thioperamide (1, 10 and 30 nM) (pA2 = 9.21 ± 0.40; slope = 1.03 ± 0.35) but it was unaffected by pyrilamine (100 nM), cimetidine (1 μM), atropine (10 μM), propranolol (1 μM), indomethacin (10 μM) or nordthydroguaiaretic acid (0.1 mM). Inhibitors of nitric oxide synthase, L-NG-monomethylarginine (L-NMMA, 10 μM) and NG-nitro-L-arginine methylester (L-NOARG, 10 μM) inhibited the relaxation effect of (R)α-MeHA, by approximately 52% and 70%, respectively). This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 μM). Methylene blue (10 μM) and ouabain (10 μM) inhibited relaxation (R)α-MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (R)α-MeHA-induced endothelium-dependent rat aorta relaxation nor are the muscarinic cholinergic and β-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na+,K+-ATPase in (R)α-MeHA-induced endothelium-dependent rat aorta relaxation.

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Selected References

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  1. Arrang J. M., Devaux B., Chodkiewicz J. P., Schwartz J. C. H3-receptors control histamine release in human brain. J Neurochem. 1988 Jul;51(1):105–108. doi: 10.1111/j.1471-4159.1988.tb04841.x. [DOI] [PubMed] [Google Scholar]
  2. Arrang J. M., Garbarg M., Lancelot J. C., Lecomte J. M., Pollard H., Robba M., Schunack W., Schwartz J. C. Highly potent and selective ligands for histamine H3-receptors. Nature. 1987 May 14;327(6118):117–123. doi: 10.1038/327117a0. [DOI] [PubMed] [Google Scholar]
  3. Arrang J. M., Garbarg M., Schwartz J. C. Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature. 1983 Apr 28;302(5911):832–837. doi: 10.1038/302832a0. [DOI] [PubMed] [Google Scholar]
  4. Bent S., Fehling U., Braam U., Schunack W., Schmutzler W. The influence of H1-, H2- and H3-receptors on the spontaneous and ConA induced histamine release from human adenoidal mast cells. Agents Actions. 1991 May;33(1-2):67–70. doi: 10.1007/BF01993129. [DOI] [PubMed] [Google Scholar]
  5. Bredt D. S., Snyder S. H. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A. 1989 Nov;86(22):9030–9033. doi: 10.1073/pnas.86.22.9030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burgaud J. L., Javellaud J., Oudart N. Bronchodilator action of an agonist for histamine H3-receptors in guinea pig perfused bronchioles and lung parenchymal strips. Lung. 1992;170(2):95–108. doi: 10.1007/BF00175981. [DOI] [PubMed] [Google Scholar]
  7. Carrier G. O., White R. E., Kirby M. L. Histamine-induced relaxation of rat aorta. Importance of H1 receptor and vascular endothelium. Blood Vessels. 1984;21(4):180–183. [PubMed] [Google Scholar]
  8. Chen G., Suzuki H., Weston A. H. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol. 1988 Dec;95(4):1165–1174. doi: 10.1111/j.1476-5381.1988.tb11752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark W. G., Moyer S. G. The effects of acetaminophen and sodium salicylate on the release and activity of leukocytic pyrogen in the cat. J Pharmacol Exp Ther. 1972 Apr;181(1):183–191. [PubMed] [Google Scholar]
  10. Coruzzi G., Poli E., Bertaccini G. Histamine receptors in isolated guinea pig duodenal muscle: H3 receptors inhibit cholinergic neurotransmission. J Pharmacol Exp Ther. 1991 Jul 1;258(1):325–331. [PubMed] [Google Scholar]
  11. Daum P. R., Downes C. P., Young J. M. Histamine-induced inositol phospholipid breakdown mirrors H1-receptor density in brain. Eur J Pharmacol. 1983 Mar 4;87(4):497–498. doi: 10.1016/0014-2999(83)90092-4. [DOI] [PubMed] [Google Scholar]
  12. Djuric D. M., Andjelkovic I. Z. The evidence for histamine H(3) receptor-mediated endothelium-dependent relaxation in isolated rat aorta. Mediators Inflamm. 1995;4(3):217–221. doi: 10.1155/S0962935195000354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ea Kim L., Javellaud J., Oudart N. 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):103–106. doi: 10.1111/j.1476-5381.1992.tb14218.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fredholm B. B., Dunwiddie T. V. How does adenosine inhibit transmitter release? Trends Pharmacol Sci. 1988 Apr;9(4):130–134. doi: 10.1016/0165-6147(88)90194-0. [DOI] [PubMed] [Google Scholar]
  15. Garbarg M., Tuong M. D., Gros C., Schwartz J. C. Effects of histamine H3-receptor ligands on various biochemical indices of histaminergic neuron activity in rat brain. Eur J Pharmacol. 1989 May 2;164(1):1–11. doi: 10.1016/0014-2999(89)90225-2. [DOI] [PubMed] [Google Scholar]
  16. Gorman R. R., Bunting S., Miller O. V. Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins. 1977 Mar;13(3):377–388. doi: 10.1016/0090-6980(77)90018-1. [DOI] [PubMed] [Google Scholar]
  17. Gryglewski R. J., Panczenko B., Korbut R., Grodzinska L., Ocetkiewicz A. Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins. 1975 Aug;10(2):343–355. doi: 10.1016/0090-6980(75)90053-2. [DOI] [PubMed] [Google Scholar]
  18. Hew R. W., Hodgkinson C. R., Hill S. J. Characterization of histamine H3-receptors in guinea-pig ileum with H3-selective ligands. Br J Pharmacol. 1990 Nov;101(3):621–624. doi: 10.1111/j.1476-5381.1990.tb14130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hill S. J. Distribution, properties, and functional characteristics of three classes of histamine receptor. Pharmacol Rev. 1990 Mar;42(1):45–83. [PubMed] [Google Scholar]
  20. Ishikawa S., Sperelakis N. A novel class (H3) of histamine receptors on perivascular nerve terminals. Nature. 1987 May 14;327(6118):158–160. doi: 10.1038/327158a0. [DOI] [PubMed] [Google Scholar]
  21. Komori K., Suzuki H. Electrical responses of smooth muscle cells during cholinergic vasodilation in the rabbit saphenous artery. Circ Res. 1987 Oct;61(4):586–593. doi: 10.1161/01.res.61.4.586. [DOI] [PubMed] [Google Scholar]
  22. Konishi M., Toda N., Yamamoto M. Different mechanisms of action of histamine in isolated arteries of the dog. Br J Pharmacol. 1981 Sep;74(1):111–118. doi: 10.1111/j.1476-5381.1981.tb09961.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Long C. J., Berkowitz B. A. What is the relationship between the endothelium derived relaxant factor and nitric oxide? Life Sci. 1989;45(1):1–14. doi: 10.1016/0024-3205(89)90429-3. [DOI] [PubMed] [Google Scholar]
  24. Luo X. X., Tan Y. H., Sheng B. H. Histamine H3-receptors inhibit sympathetic neurotransmission in guinea pig myocardium. Eur J Pharmacol. 1991 Nov 12;204(3):311–314. doi: 10.1016/0014-2999(91)90857-m. [DOI] [PubMed] [Google Scholar]
  25. Malinowska B., Schlicker E. H3 receptor-mediated inhibition of the neurogenic vasopressor response in pithed rats. Eur J Pharmacol. 1991 Dec 3;205(3):307–310. doi: 10.1016/0014-2999(91)90915-d. [DOI] [PubMed] [Google Scholar]
  26. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  27. Martinez-Mir M. I., Pollard H., Moreau J., Arrang J. M., Ruat M., Traiffort E., Schwartz J. C., Palacios J. M. Three histamine receptors (H1, H2 and H3) visualized in the brain of human and non-human primates. Brain Res. 1990 Sep 3;526(2):322–327. doi: 10.1016/0006-8993(90)91240-h. [DOI] [PubMed] [Google Scholar]
  28. McKinney M., Bolden C., Smith C., Johnson A., Richelson E. Selective blockade of receptor-mediated cyclic GMP formation in N1E-115 neuroblastoma cells by an inhibitor of nitric oxide synthesis. Eur J Pharmacol. 1990 Mar 13;178(1):139–140. doi: 10.1016/0014-2999(90)94807-a. [DOI] [PubMed] [Google Scholar]
  29. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moritoki H., Tanioka A., Maeshiba Y., Iwamoto T., Ishida Y., Araki H. Age-associated decrease in histamine-induced vasodilation may be due to reduction of cyclic GMP formation. Br J Pharmacol. 1988 Dec;95(4):1015–1022. doi: 10.1111/j.1476-5381.1988.tb11734.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mülsch A., Busse R. NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):143–147. doi: 10.1007/BF00195071. [DOI] [PubMed] [Google Scholar]
  32. North R. A. Twelfth Gaddum memorial lecture. Drug receptors and the inhibition of nerve cells. Br J Pharmacol. 1989 Sep;98(1):13–28. doi: 10.1111/j.1476-5381.1989.tb16855.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Oike M., Kitamura K., Kuriyama H. Histamine H3-receptor activation augments voltage-dependent Ca2+ current via GTP hydrolysis in rabbit saphenous artery. J Physiol. 1992 Mar;448:133–152. doi: 10.1113/jphysiol.1992.sp019033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  35. Rapoport R. M., Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res. 1983 Mar;52(3):352–357. doi: 10.1161/01.res.52.3.352. [DOI] [PubMed] [Google Scholar]
  36. Rosic M., Collis C. S., Anjelkovic I. Z., Segal M. B., Djuric D., Zlokovic B. V. The effects of (R) alpha-methyl histamine on the isolated guinea pig aorta. Agents Actions Suppl. 1991;33:283–287. doi: 10.1007/978-3-0348-7309-3_19. [DOI] [PubMed] [Google Scholar]
  37. Schwörer H., Katsoulis S., Racké K. Histamine inhibits 5-hydroxytryptamine release from the porcine small intestine: involvement of H3 receptors. Gastroenterology. 1992 Jun;102(6):1906–1912. doi: 10.1016/0016-5085(92)90312-m. [DOI] [PubMed] [Google Scholar]
  38. Tateson J. E., Moncada S., Vane J. R. Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins. 1977 Mar;13(3):389–397. doi: 10.1016/0090-6980(77)90019-3. [DOI] [PubMed] [Google Scholar]
  39. Van de Voorde J., Leusen I. Effect of histamine on aorta preparations of different species. Arch Int Pharmacodyn Ther. 1984 Mar;268(1):95–105. [PubMed] [Google Scholar]
  40. Van de Voorde J., Leusen I. Role of the endothelium in the vasodilator response of rat thoracic aorta to histamine. Eur J Pharmacol. 1983 Jan 28;87(1):113–120. doi: 10.1016/0014-2999(83)90056-0. [DOI] [PubMed] [Google Scholar]
  41. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  42. Woolfson R. G., Poston L. Effect of NG-monomethyl-L-arginine on endothelium-dependent relaxation of human subcutaneous resistance arteries. Clin Sci (Lond) 1990 Sep;79(3):273–278. doi: 10.1042/cs0790273. [DOI] [PubMed] [Google Scholar]

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