The Intermediation Role of Central Cyclooxygenase Products Txa2, Pgf2α, Pge, and PGD in Orexin-Evoked Cardiovascular Effects

Abstract

Centrally injected some prostaglandins (PG) and orexin (OX) produce similar cardiovascular responses.We have recently reported that both central cyclooxygenase (COX) and central lipoxygenase (LOX) enzymes mediate the cardiovascular effects of OX. In the current study, we aimed to investigate the mediating effects of thromboxane (TX) A 2 , PGD, PGE, and PGF 2a , as COX pathway subproducts known to be active in cardiovascular control, on cardiovascular responses elicited by OX. Intracerebroventricular (i.c.v.) injection of OX increased cardiovascular levels in normotensive male Sprague Dawley rats. Moreover, central pretreatment with the TXA 2 synthesis inhibitor furegrelate, PGF 2α receptor antagonist, PGF 2α -dimethylamine, PGE, and PGD receptor antagonist AH6809 partially attenuated the centrally administered OX -induced pressor and tachycardic cardiovascular responses in rats.In conclusion, our results show that i.c.v. injection of OX increases blood pressure and heart rate. Moreover, TXA 2 , PGF 2α , PGE, and PGD mediate, at least in part, the centrally applied OX -evoked pressor and tachycardic responses. The results suggest that centrally injected OX -evoked pressor and tachycardia responses may also be mediated by arachidonic acid metabolites other than TXA 2 , PGF 2α , PGE, and PGD. HighlightsCentral injection of OX augments MAP and HR.The TXA 2 mediates the OX-produced cardiovascular responses.The central PGF 2a intermediates the OX-produced cardiovascular responses.The central PGE and PGD are involved in the OX-produced cardiovascular responses. et al. 1999). On the other hand, previous studies in this research area have reported that the OX-evoked cardiovascular effects are mediated by the vasopressinergic (Al-Barazanji et al. 2001), renin-angiotensin (Lin et al. 2002), cholinergic (Antunes et al. 2001), and histaminergic systems (Jochem 2009.AA released from membrane phospholipids by activation of phospholipase A 2 (PLA 2 ) forms prostaglandins (PG) or leukotrienes via the COX or lipoxygenase LOX enzyme pathway (Smith et al. 2000;Wlodawer and Samuelsson 1973). In previous studies, researchers have documented that AA and its metabolites are involved in cardiovascular control (Tassoni et al. 2008). Centrally injected melittin, PLA 2 activator and AA increased arterial pressures in normotensive and hypotensive rats (Yalcin and Erturk 2007; Yalcin and Aydin 2009;). It could be considered that centrally injected melittin-or AA -induced cardiovascular responses are the result of possibly central COX pathway products. This is because it is known that as AA -COX pathway products centrally PGE 2 ,