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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.

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Previously, we showed that central injection of melittin, a phospholipase A2 activator, arachidonic acid (AA) or U‐46619, a thromboxane A2 analog, caused pressor effects. Moreover centrally injected histamine leads to pressor response by activating central histamine receptors. In the present study, it was aimed to demonstrate interaction between central prostaglandinergic and histaminergic system on central regulation of cardiovascular system by activating prostaglandin cascade with central administration of melittin or AA.Experiments were performed in male Spraque Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin or AA caused dose‐ and time‐dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Also, melittin or AA accompanied by 28 % or 56 % increase in extracellular histamine concentration in the posterior hypothalamus, respectively as shown in microdialysis studies. Moreover, H2 receptor antagonist ranitidine almost completely and H3/H4 receptor antagonist thioperamide partly blocked melittin‐evoked cardiovascular effects, whereas H1 receptor blocker chlorpheniramine had no effect.In conclusion, obtained first data show that there is an interaction between central histaminergic and prostaglandin cascade to central regulate cardiovascular system.This study was supported by grants from TUBITAK (110O878).