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.
Highlights
Histamine is present in essentially all tissues and it can stimulate all three classes of histamine receptors
The histamine H1 and H2 receptor-mediated actions of histamine on effector cells are linked with the (C) 1996 Rapid Science Publishers accumulation of cGMP, inositol phospholipids and cAMP, respectively.[4,5,6]
The influence of endothelium on responses to histamine and (R)a-MeHA: Histamine (0.1 nM0.01mM) induced concentration-dependent relaxation of phenylephrine (300 nM)-precontracted rat aorta with intact endothelium, reaching approximately 70% of the papaverineinduced maximum relaxation (0.1mM). 7.98 _+ 0.02)
Summary
Histamine is present in essentially all tissues and it can stimulate all three classes of histamine receptors. It is found in significant concentrations in the blood and in the vessel walls. It has been known for several years that histamine receptor subtypes vary in different, isolated vascular tissues, depending upon the anatomic location, species and physiological response. It is known that two types of histamine receptors, H1 and H2, participate in vascular responses to histamine.[2] Intravascular administration of histamine elicits a concentration-dependent fall in blood pressure in most species. The histamine H1 and H2 receptor-mediated actions of histamine on effector cells are linked with the (C) 1996 Rapid Science Publishers accumulation of cGMP, inositol phospholipids and cAMP, respectively.[4,5,6] In different blood vessels cGMP formation is activated by endothelium-derived relaxing factor (EDRF)[7] while cAMP formation is stimulated by prostacyclin (PGI2).8’9
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