2. Academic Validation
  3. Endogenous ET-1 promotes ANP secretion through activation of COX2-L-PGDS-PPARγ signaling in hypoxic beating rat atria

Endogenous ET-1 promotes ANP secretion through activation of COX2-L-PGDS-PPARγ signaling in hypoxic beating rat atria

  • Peptides. 2019 Dec;122:170150. doi: 10.1016/j.peptides.2019.170150.
Xiang Li 1,  Zhuo-Na Han 1,  Ying Liu 1,  Lan Hong 1,  Bai-Ri Cui 2,  Xun Cui 3
Affiliations

Affiliations

  • 1 Department of Physiology, School of Medical Sciences, Yanbian University, Yanji, 133-002, China.
  • 2 Institute of Clinical Medicine, Yanbian University, Yanji, 133-000, China. Electronic address: [email protected].
  • 3 Department of Physiology, School of Medical Sciences, Yanbian University, Yanji, 133-002, China; Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133-002, China; Cellular Function Research Center, Yanbian University, Yanji, 133-002, China. Electronic address: [email protected].
PMID: 31541683 DOI: 10.1016/j.peptides.2019.170150
Abstract

Endothelin-1 (ET-1) is a potent stimulus for the secretion of atrial natriuretic peptide (ANP) and hypoxia stimulates the release of ET-1, which is involved in the regulation of atrial ANP secretion. However, the precise mechanism of endogenous ET-1 in the regulation of hypoxia-induced ANP secretion is unclear. Therefore, this study aimed to investigate the mechanism of hypoxia-induced endogenous ET-1 regulation of ANP secretion in isolated perfused hypoxic beating rat atria. The results of this study showed that acute hypoxia significantly stimulated ET-1 release and upregulated the expression of its type A as well as type B receptors (ETA and ETB receptors). Endogenous ET-1 induced by hypoxia markedly upregulated the expression of cyclooxygenase 2 (COX2) through activation of its two receptors, leading to an increase in lipocalin-type prostaglandin D synthase (L-PGDS) expression and prostaglandin D2 (PGD2) production. L-PGDS-derived PGD2 activated Peroxisome Proliferator-activated Receptor γ (PPARγ), ultimately promoting hypoxia-induced ANP secretion. Conversely, L-PGDS-derived PGD2 may in turn regulate L-PGDS expression by a nuclear factor erythroid-2-related factor 2 (NRF2)-mediated feedback mechanism. These results indicate that endogenous ET-1 induced by hypoxia promotes hypoxia-induced ANP secretion by activation of COX2-L-PGDS-PPARγ signaling in beating rat atria. In addition, the positive feedback loop between L-PGDS-derived PGD2 and L-PGDS expression induced by hypoxia is part of the mechanism of hypoxia-induced ANP secretion by endogenous ET-1.

Keywords

Atrial natriuretic peptide; Cyclooxygenase 2; Endothelin-1; Hypoxia; Lipocalin-type prostaglandin D synthase.

Figures
Products