Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D in the beating rat atrium.

Prostaglandin D (PGD) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGD in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether PGD can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. PGD (0.1 to 10 µM) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of PGD on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 (1.0 µM) and AL-8810 (1.0 µM), PGD and prostaglandin F2α (PGF2α) receptor antagonists, respectively. Moreover, PGD clearly upregulated atrial peroxisome proliferator-activated receptor gamma (PPARγ) and the PGD metabolite 15-deoxy-Δ12,14-PGJ (15d-PGJ, 0.1 µM) dramatically increased atrial ANP secretion. Increased ANP secretions induced by PGD and 15d-PGJ were completely blocked by the PPARγ antagonist GW9662 (0.1 µM). PD98059 (10.0 µM) and LY294002 (1.0 µM), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by PGD. These results indicated that PGD stimulated atrial ANP secretion and promoted positive inotropy by activating PPARγ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating PGD-induced atrial ANP secretion.