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We previously reported that intracerebroventricularly (ICV) injected arachidonic acid (AA) could produce pressor and bradycardic responses on the cardiovascular system and hyperventilation effect on the respiratory system by activating cyclooxygenase (COX). We also demonstrated that centrally injected AA-induced cardiovascular and respiratory responses were mediated by COX-metabolites, such as thromboxane A2 (TXA2), prostaglandin (PG) D, PGE, and PGF2α. Brain tissue is also able to express the lipoxygenase (LOX) enzyme and LOX-induced AA-metabolites. The current study was designed to investigate the possible mediation of the central LOX pathway in AA-induced cardiorespiratory effects in anesthetized rats. Central pretreatment with different doses of a non-selective LOX inhibitor, nordihydroguaiaretic acid (NDGA) (500 and 1000 μg; ICV) partially blocked the AA (0.5 μmol; ICV)-evoked pressor and bradycardic cardiovascular responses in male anesthetized Sprague Dawley rats. Pretreatment with different doses of NDGA (500 and 1000 μg; ICV) also reduced AA-induced hyperventilation responses, with an increase in tidal volume, respiratory rate and minute ventilation, in the rats. Moreover, AA-induced increasing pO2 and decreasing pCO2 responses were diminished by central NDGA pretreatment. In summary, our findings show that the central LOX pathway might mediate, at least in part, centrally administered AA-evoked cardiorespiratory and blood gases responses.

Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the phospholipids of the cell membranes of the body and is abundant in the brain. Exogenously administered AA has been shown to affect brain metabolism and to exhibit cardiovascular and neuroendocrine actions. However, little is known regarding its respiratory actions and/or central mechanism of its respiratory effects. Therefore, the present study was designed to investigate the possible effects of centrally injected AA on respiratory system and the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway on AA-induced respiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA induced dose- and time-dependent increase in tidal volume, respiratory rates and respiratory minute ventilation and also caused an increase in partial oxygen pressure (pO2) and decrease in partial carbon dioxide pressure (pCO2) in male anaesthetized Sprague Dawley rats. I.c.v. pretreatment with ibuprofen, a non-selective COX inhibitor, completely blocked the hyperventilation and blood gases changes induced by AA. In addition, central pretreatment with different doses of furegrelate, a TXA2 synthesis inhibitor, also partially prevented AA-evoked hyperventilation and blood gases effects. These data explicitly show that centrally administered AA induces hyperventilation with increasing pO2 and decreasing pCO2 levels which are mediated by the activation of central COX to TXA(2) signaling pathway. (C) 2016 Elsevier B.V. All rights reserved.