Histamine receptor type coupled to nitric oxide‐induced relaxation of guinea‐pig nasal mucosa

Abstract

1 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. 2 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 microM. Neither dimaprit (H2-receptor selective) nor R-alpha-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 microM. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulated relaxation of nasal mucosae. KB values for chlorpheniramine (0.87 nM) and diphenhydramine (7.4 nM) were consistent with their interaction at the H1-receptor type. Additionally, neither 10 microM cimetidine (H2-receptor selective) nor 1 microM thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. 4 In the presence of 10 microM indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 +/- 5% of the noradrenaline-induced tone with an EC50 value of 2.9 +/- 0.2 microM, which was not different from control values (EC50 = 5.0 +/- 0.4 microM; maximal relaxation = 71 +/- 6%). In contrast, 200 microM NG-nitro-L-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal mucosae. 5 In conclusion, data from the present study suggest only the H1-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.

The low-dose combination preparation Vertigoheel activates cyclic nucleotide pathways and stimulates vasorelaxation

“…This notion is in line with clinical experiences that have by and large demonstrated the effectiveness of pharmacological approaches with histamine analogs [5] or phytotherapeutic interventions with Ginkgo biloba [47] or Vertigoheel [16] for the treatment of dizziness and vertigo. The standard antivertiginous drug betahistine causes vasodilation through its histaminergic action [3,29]. Betahistine acts as a potent cerebral microcirculatory vasodilator in humans when given orally [42] and was shown to specifically increase cochlear blood flow in guinea pigs [23], consolidating the notion of a causal link between vertigo and impaired microvascular blood flow.…”

Orale Antihistaminika der 2. Generation bei allergischer Rhinitis

“…Im Tierversuch ist die Relaxation glatter Muskelzellen in der Nasenschleimhaut[45] bzw. Weitstellung nasaler Sinusoide auch durch Vorbehandlung mit einem NO-Antagonisten hemmbar[46], beim Menschen konnte jedoch kein solcher Effekt gezeigt werden[47 ± 49].…”