Histamine release from mast cells is a primary mediator of
rhinorrhea, nasal mucosal swelling, increased secretion,
sneezing,
pruritus and congestion that occur in
allergic rhinitis. It is well known that
histamine H(1) receptor antagonists inhibit the itch and rhinorhea, but do not block the allergic nasal congestion. A growing body of evidence shows that in addition to
histamine H(1) receptors, activation of H(3) receptors may contribute to the procongestant nasal actions of
histamine. Activation of the prejunctional
histamine H(3) receptor modulates sympathetic control of nasal vascular tone and resistance. The present study was conducted to further characterize the role of
histamine H(3) receptors on neurogenic sympathetic vascular contractile responses in isolated porcine nasal turbinate mucosa. We presently found that the
histamine H(3) receptor agonist, (R)-
alpha-methylhistamine (10-1000 nM), inhibited electrical field stimulation-induced sympathetic vasomotor contractions in a concentration-dependent fashion. Pretreatment with either of the selective
histamine H(3) receptor antagonists,
thioperamide and
clobenpropit, blocked the sympathoinhibitory effect of (R)-
alpha-methylhistamine in porcine turbinate mucosa. The effect of
compound 48/80, an agent that elicits the release of endogenous
histamine from mast cells on nasal sympathetic contractile responses, was also tested. The action of
compound 48/80 to release mast cell-derived
histamine in the nose mimics many of the nasal responses associated with
allergic rhinitis, extravascular leakage and decreased nasal patency. We presently found that
compound 48/80 also inhibited the electrical field stimulation-induced sympathetic response. Pretreatment with the H(3) receptor antagonist
clobenpropit blocked the sympathoinhibitory action of
compound 48/80 on sympathetic contractile responses in nasal mucosa. Taken together, these studies indicate that
histamine H(3) receptors modulate vascular contractile responses by inhibition of
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 allergic nasal congestive disease.