Usage Information
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.
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
Usage data is cumulative from January 2025 through January 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 683 | 191 |
| 105 | 44 | |
| Figure | 388 | 8 |
| Supplemental data | 63 | 2 |
| Citation downloads | 51 | 0 |
| Totals | 1,290 | 245 |
| Total Views | 1,535 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
