Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic vasoconstriction.

Abstract The peripheral histamine H 3 receptor is a presynaptic heterologous receptor located on postganglionic sympathetic nerve fibers innervating sympathetic effector systems such as blood vessels and the heart. An extensive body of evidence shows that activation of the histamine H 3 receptor attenuates sympathetic tone by presynaptic inhibition of noradrenaline release. It is proposed that this sympathoinhibitory action, in vivo, leads to reduced vasoconstriction, thereby eliciting a vasodilatory effect. In humans, the peripheral histamine H 3 receptor has also been shown to exert a sympathoinhibitory function on specific peripheral autonomic effector systems. For example, human saphenous vein and heart possess functional presynaptic histamine H 3 receptors on the sympathetic nerve terminals that upon activation decrease the sympathetic tone to these respective organs. The present studies were conducted to define the role of histamine H 3 receptors on neurogenic sympathetic vasoconstrictor responses in human nasal turbinate mucosa. Contractility studies were conducted to evaluate the effect of histamine H 3 receptor activation on sympathetic vasoconstriction in surgically isolated human nasal turbinate mucosa. We found that the histamine H 3 receptor agonist, ( R )-α-methylhistamine (30 and 300 nM), inhibited electrical field stimulation-induced (neurogenic) sympathetic vasoconstriction in a concentration-dependent fashion. Pretreatment with the selective histamine H 3 receptor antagonist, clobenpropit (100 nM), blocked the sympathoinhibitory effect of ( R )-α-methylhistamine on the neurogenic sympathetic vasoconstriction. In addition, analysis of Taqman mRNA expression studies showed a specific, high level of distribution of the histamine H 3 receptor localized in the human nasal mucosa. Taken together, these studies indicate that histamine H 3 receptors modulate vascular contractile responses in human nasal mucosa most likely by inhibiting noradrenaline release from sympathetic nerve terminals in nasal mucosa. It is further suggested that histamine H 3 receptors may play a role in the regulation of vascular tone and nasal patency in histamine-dependent allergic nasal congestive disease.