Effect Of ET-1-L-PGDS-PPAR? Signaling Pathway On Hypoxia-induced ANP Secretion In Beating Rat Atria

Aims:Lipocalin-type prostaglandin D synthase(L-PGDS)and peroxisome proliferator activated receptor y(PPARy)play important roles in cardiovascular diseases.At present,studies have shown that L-PGDS and PPARy have a protective effect on the heart during hypoxia and ischemia.Nevertheless,effects of hypoxia-inducible factor endothelin-1(ET-1)on L-PGDS and PPARy protein levels and its role in hypoxia-induced atrial natriuretic peptide(ANP)secretion are unclear.Therefore,in this study,isolated rat atrial beating device was used to prepare acute hypoxia model to investigate the effect of ET-1 on L-PGDS-PPARy signaling and its role in the regulation of hypoxia-induced atrial ANP secretion.Methods:Acute hypoxia atrial model was prepared in isolated rat atrial beating perfusion device by replacing Oxygen with Nitrogen.Levels of immunoreactive ANP in perfusates were measured with specific radioimmunoassays.The level of PGD2 in rat atrial perfusate was measured by enzyme-linked immunosorbent assay.Western blotting was used to analyze the expression changes of protein content.Results:Hypoxia significantly increased ET-1 release and stimulated ANP secretion,while upregulating L-PGDS and PPAR?.BQ123,a type-A receptor antagonist of ET-1,and BQ788,a type-B receptor antagonist,not only inhibited hypoxia-induced upregulation of L-PGDS and PPARy but also inhibited the increase of hypoxia-induced atrial COX2 protein and PGD2 content.In addition,hypoxia-induced ANP secretion was strongly attenuated by BQ123 and BQ788.L-PGDS inhibitors AT-56 and HQL-49 also mimic the effects of BQ123 and BQ788.Conclusion:Endogenous ET-1 promotes ANP secretion by activation of L-PGDS-PPAR?signaling in beating rat hypoxic atria.