Endothelial Cell Prostaglandin E2 Receptor EP4 is Essential for Blood Pressure Homeostasis

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2020 Jul 10

PMID 32641583

Citations 21

Authors

Hu Xu

Bingying Fang

Shengnan Du

Sailun Wang

Qingwei Li

Xiao Jia

Chengzhen Bao

Lan Ye

Xue Sui

Lei Qian

Zhilin Luan

Guangrui Yang

Feng Zheng

Nanping Wang

Lihong Chen

Xiaoyan Zhang

Youfei Guan

Affiliations

Soon will be listed here.

Abstract

Prostaglandin E2 and its cognate EP1-4 receptors play important roles in blood pressure (BP) regulation. Herein, we show that endothelial cell-specific (EC-specific) EP4 gene-knockout mice (EC-EP4-/-) exhibited elevated, while EC-specific EP4-overexpression mice (EC-hEP4OE) displayed reduced, BP levels compared with the control mice under both basal and high-salt diet-fed conditions. The altered BP was completely abolished by treatment with l-NG-nitro-l-arginine methyl ester (l-NAME), a competitive inhibitor of endothelial nitric oxide synthase (eNOS). The mesenteric arteries of the EC-EP4-/- mice showed increased vasoconstrictive response to angiotensin II and reduced vasorelaxant response to acetylcholine, both of which were eliminated by l-NAME. Furthermore, EP4 activation significantly reduced BP levels in hypertensive rats. Mechanistically, EP4 deletion markedly decreased NO contents in blood vessels via reducing eNOS phosphorylation at Ser1177. EP4 enhanced NO production mainly through the AMPK pathway in cultured ECs. Collectively, our findings demonstrate that endothelial EP4 is essential for BP homeostasis.

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