Thioperamide, a histamine H3-receptor blocker, facilitates vasopressor response to footshocks.

OBJECTIVE AND

DESIGN

We assessed the functional role of the histamine H3-receptor in conscious intact rats during activation of the sympathoadrenal axis.

MATERIAL: Male Sprague-Dawley rats, with or without cerebroventricular cannula, were subjected to mild footshocks and mean arterial pressure (MAP) and heart rate were determined using a tail-cuff plethysmograph.

TREATMENTS: Saline, phentolamine (3 mg/kg, i.p.), (R)-alphafluoromethylhistidine (AFMH) (100 mg/kg, i.p., or 100 microg/5 microl, i.v.t.), (R)-alphamethylhistamine (AMH) (2 mg/kg, i.p. or 100 microg/5 microl, i.v.t.), thioperamide (THIO) (1 or 2 mg/kg, i.p., or 100 microg/5 microl, i.v.t.), mepyramine (10 mg/kg, i.p.), cimetidine (2 mg/kg, i.p.).

METHODS

Urinary catecholamines were determined by fluorometry. Statistical differences between experimental groups were evaluated by Student's t-test or one-way ANOVA.

RESULTS

Footshocks increased both MAP and heart rate. The vasopressor response to footshocks was facilitated (p < 0.001) by i.p. administration of AFMH, a histidine decarboxylase inhibitor, or THIO, a H3-receptor antagonist, but not by i.v.t. injection of these drugs. AMH, a H3-receptor agonist, given i.p., decreased the vasopressor response to footshocks (p < 0.001). This action of AMH was abolished by THIO but not by mepyramine or cimetidine. The MAP response to exogenous norepinephrine was not altered by i.p. administration of either AFMH or THIO.

CONCLUSIONS

Our results demonstrate an involvement of peripheral histamine H3 prejunctional receptors in the inhibitory modulation of peripheral noradrenergic responses during stress.