The aim of this study was to characterize the histamine receptor type mediating relaxation of the vascular bed of the nasal mucosa from the guinea-pig, and to determine the role of cyclo-oxygenase products and nitric oxide in this relaxant response to histamine. These studies were performed in isolated nasal mucosae examined in vitro to obtain potencies of histamine receptor-type selective agonists in causing vasorelaxation and to determine affinities of histamine receptor antagonists for inhibiting histamine-induced relaxation. After contraction of nasal mucosae with noradrenaline, histamine caused a maximal relaxation response that was 75 ± 6% of the contraction caused by noradrenaline with a mean EC50 value of 4.3 ± 0.5 μM. Neither dimaprit (H2-receptor selective) nor R-α-methylhistamine (H3-receptor selective) caused significant relaxation of nasal mucosae. In contrast, betahistine (H1-receptor selective) caused an 81 ± 7% relaxation of noradrenaline-induced tone with an EC50 value of 15 ± 1 μM. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulate relaxation of nasal mucosae. K B values for chlorpheniramine (0.87 nM) and diphenhydramine (7.4 nM) were consistent with their interaction at the Hi-receptor type. Additionally, neither 10 μM cimetidine (H2-receptor selective) nor 1 μM thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. In the presence of 10 μM indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 ± 5% of the noradrenaline-induced tone with an EC5O value of 2.9 ± 0.2 μM, which was not different from control values (EC 50 = 5.0 ± 0.4 μM; maximal relaxation = 71 ± 6%). In contrast, 200 μM NG-nitro-L-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal mucosae. In conclusion, data from the present study suggest only the H 1-receptor type mediates relaxation of nasal mucosal blood vessels to histamine, and histamine-induced relaxation of nasal mucosae is entirely dependent on nitric oxide production.
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