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.

Alpha-fluoromethylhistidine, an inhibitor of histamine biosynthesis, causes arterial hypertension.

In this study we assessed the cardiovascular response to 13 days of irreversible inhibition of the enzyme histidine-decarboxylase (HD) with alpha-fluoro-methylhistidine (AFMH). Age-matched untreated rats were used as controls, Tail-cuff mean arterial pressure (MAP) and heart rate (HR) rose progressively in AFMH-treated rats, reaching maximal values during the study period by the 13th day of treatment. There was a reduction in urinary histamine at the day 7 and 13, and of sodium excretion at the day 7 of treatment, while the renal catecholamine excretion was increased at both days of treatment, suggesting an increase of sympathetic activity. At the 13th day of treatment, there was an activation of the renin-angiotensin-aldosterone system. In addition, the cardiovascular responses to footshock stress were determined in rats treated intraperitoneally (i.p.) or intracerebroventricularly (i.v.t.) with a single dose of AFMH. Peripheral sympathetic facilitation was found, as the hemodynamic response to footshock stress was significantly enhanced after i.p. administration, but not after i.v.t. administration of AFMH. Our results suggest that conditions of peripheral histamine deficiency may result in sympathetic facilitation, arterial hypertension and tachycardia in the rat.