MERKEZİ SİKLOKSİJENAZ ÜRÜNLERİ TXA2, PGF2α, PGE VE PGD’NİN OREKSİN’İN OLUŞTURDUĞU KARDİYOVASKÜLER ETKİLERDEKİ ARACILIĞI

Merkezi olarak enjekte edilen bazı prostaglandinler (PG) ve oreksin (OX) benzer kardiyovasküler yanıtlara sahiptir. Yakın zamanda hem merkezi siklooksijenaz (COX) hem de merkezi lipoksijenaz enzimlerinin OX'nin kardiyovasküler etkilerine aracılık ettiğini bildirdik. Bu çalışmada, kardiyovasküler kontrolde aktif olduğu bilinen COX yolağı ürünleri tromboksan (TX) A2, PGD, PGE ve PGF2α'nın OX'in tarafından oluşturulan kardiyovasküler etkilerdeki aracılıklarını araştırmayı amaçladık. İntraserebroventriküler (i.c.v.) OX enjeksiyonu, normotansif erkek Sprague Dawley sıçanlarda kardiyovasküler yanıtları arttırdı. Ayrıca, TXA2 sentez inhibitörü furegrelate, PGF2α reseptör antagonisti, PGF2α-dimetilamin, PGE ve PGD reseptör antagonisti AH6809 ile merkezi ön tedavi, sıçanlarda merkezi olarak uygulanan OX ile indüklenen pressör ve taşikardik kardiyovasküler yanıtları kısmen zayıflattı. Sonuç olarak, verilerimiz i.c.v. OX enjeksiyonunun kan basıncını ve kalp atım hızını artırdığını göstermektedir. Ayrıca, TXA2, PGF2α, PGE ve PGD kısmende olsa, merkezi olarak uygulanan OX ile uyarılmış pressör ve taşikardik yanıtlara aracılık etmektedir. Sonuçlar, merkezi olarak enjekte edilen OX ile uyarılmış pressör ve taşikardik yanıtlara, TXA2, PGF2α, PGE ve PGD dışındaki araşidonik asit metabolitlerinin de aracılık edebileceğini göstermektedir.

Anahtar Kelimeler:

Oreksin, Tromboksan A2, Prostaglandin F2α, Prostaglandin E, Prostaglandin D

THE INTERMEDIATION ROLE OF CENTRAL CYCLOOXYGENASE PRODUCTS TXA2, PGF2Α, PGE, AND PGD IN OREXIN-EVOKED CARDIOVASCULAR EFFECTS

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 PGF2, 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.

Keywords:

Orexin, Thromboxane A2, Prostaglandin F2α, Prostaglandin E, Prostaglandin D,

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