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The purpose of the current study is to investigate the functional connections between the central histaminergic and cholinergic systems at NTS level in hypotensive condition. Experiments were carried out in male Wistar Albino rats. The hypotension was achieved by withdrawing a total volume of 1.5 ml blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in NTS area to measure extracellular ACh and Ch levels. The hemorrhage produced a severe and long-lasting decrease in mean arterial blood pressure (MAP) and increase in extracellular ACh and Ch levels in NTS. Administration of histamine intracerebroventricularly (i.c.v.) or into the NTS reversed the hemorrhagic hypotension by increasing MAP and heart rate. I.c.v. injection of histamine also caused the additional increase in extracellular ACh and Ch levels. Moreover, central histamine injection augmented intracytoplasmic AChE immunoreactivity in NTS. These changes were completely blocked by histaminergic H1 receptor antagonist chlorpheniramine, but histaminergic H2 receptor blocker ranitidine and histaminergic H3/H4 receptor antagonist thioperamide failed to produce these effects. In conclusion, these findings are interpreted that brain histaminergic H1 receptor activation by central histamine injection may promote cholinergic stimulation in the NTS and subsequently reverses the hypotension.

The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague–Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3–H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A 2 . Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A 2 (TXA 2 ) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H 2 receptor antagonist ranitidine (50nmol; i.c.v.) almost completely and H 3 /H 4 receptor antagonist thioperamide (50nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H 1 receptor blocker chlorpheniramine (50nmol; i.c.v.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects.