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Mediators of Inflammation
Volume 5 (1996), Issue 1, Pages 69-74

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

Institute of Physiology, Medical Faculty University of Belgrade, Visegradska 26/II, P.O. Box 783, Belgrade 11000, Serbia

Copyright © 1996 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.