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) A2, PGD, PGE, and PGF2a, 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 TXA2 synthesis inhibitor furegrelate, PGF2α receptor antagonist, PGF2α-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, TXA2, PGF2α, 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 TXA2, PGF2α, PGE, and PGD.