Complex Role for E-Prostanoid 4 Receptors in Hypertension.


Background Prostaglandin E2 ( PGE 2) is a major prostanoid with multiple actions that potentially affect blood pressure ( BP ). PGE 2 acts through 4 distinct E-prostanoid ( EP ) receptor isoforms: EP 1 to EP 4. The EP 4 receptor ( EP 4R) promotes PGE 2-dependent vasodilation, but its role in the pathogenesis of hypertension is not clear. Methods and Results To address this issue, we studied mice after temporal- and cell-specific deletion of EP 4R. First, using a mouse line with loss of EP 4 expression induced universally after birth, we confirm that EP 4R mediates a major portion of the acute vasodilatory effects of infused PGE 2. In addition, EP 4 contributes to control of resting BP , which was increased by 5±1 mm Hg in animals with generalized deficiency of this receptor. We also show that EP 4 is critical for limiting elevations in BP caused by high salt feeding and long-term infusion of angiotensin II . To more precisely identify the mechanism for these actions, we generated mice in which EP 4R loss is induced after birth and is limited to smooth muscle. In these mice, acute PGE 2-dependent vasodilation was attenuated, indicating that this response is mediated by EP 4R in vascular smooth muscle cells. However, absence of EP 4R only in this vascular compartment had a paradoxical effect of lowering resting BP , whereas the protective effect of EP 4R on limiting angiotensin II-dependent hypertension was unaffected. Conclusions Taken together, our findings support a complex role for EP 4R in regulation of BP and in hypertension, which appears to involve actions of the EP 4R in tissues beyond vascular smooth muscle cells.





Published Version (Please cite this version)


Publication Info

Herrera, Marcela, Ting Yang, Matthew A Sparks, Michael W Manning, Beverly H Koller and Thomas M Coffman (2019). Complex Role for E-Prostanoid 4 Receptors in Hypertension. Journal of the American Heart Association, 8(4). p. e010745. 10.1161/JAHA.118.010745 Retrieved from

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Ting Yang

Assistant Professor of Medicine

Matthew A. Sparks

Associate Professor of Medicine

I serve as the Program Director for the Nephrology Fellowship Program. My goal is to work with each fellow to ensure they develop a successful career in whatever direction they choose. I am the lead for the newly established Society for Early Education Scholars (SEEDS) in the Department of Medicine. The SEEDS Program is a year-long mentored education program designed for fellows planning careers as clinician educators or education scholars.

Nephrology Fellowship Program

My interest is in finding ways to promote medical education. My focus is on leveraging social media to enhance learning in nephrology. I serve as the associate director for the Nephrology Social Media Collective (NSMC) internship and member of the board of directors of nephrology journal club (NephJC), a non-profit organization dedicated to enhancing free online medical education in nephrology. I am also co-founder and advisory board member of the first nephrology blog associated with a journal- AJKD blog, the official blog of the American Journal of Kidney Diseases. Co-creator of the popular educational project NephMadness. Past deputy editor of Renal Fellow Network where I continue to remain as faculty lead. I am currently a member of the Nephrology Board of the American Board of Internal Medicine, the Scientific and Clinical Education Lifelong learning Committee Chair, Kidney in Cardiovascular Disease Council of the American Heart Association and am a fellow of the American Society of Nephrology, the American Heart Association, and the National Kidney Foundation. 

Listen to my podcast "The Nephron Segment"

@Nephro_Sparks on X


Michael Wayne Manning

Associate Professor of Anesthesiology

Dr. Michael W. Manning, MD, Ph.D., is an Associate Professor at Duke University Medical Center, within the Divisions of Cardiothoracic and General, Vascular, and Transplant anesthesia. He serves as the director of Enhanced Recovery after Surgery programs and the director of research for the Perioperative Medicine Fellowship at Duke. His clinical practice focuses on high-risk cardiac surgery, Heart, Lung, and Liver transplantation.

Dr. Manning earned a Ph.D. in cardiovascular physiology from the University of Kentucky, where he studied the role of Angiotensin II-mediated inflammation in the development of abdominal aortic aneurysms. After graduate school, Dr. Manning remained at the University of Kentucky, earning his MD degree. He completed a year of general surgery residency before switching to anesthesia. Following residency, Dr. 
Manning continued his clinical training at Duke University with a one-year clinical fellowship in Adult Cardiothoracic Anesthesiology and a 2-year research fellowship. He joined the Duke faculty in 2014. 

His current research interests are ERAS centered, specifically in the role of opioid-free anesthesia and goal-directed fluid therapy in cardiac surgery on renal outcomes.


Thomas Myron Coffman

James R. Clapp Distinguished Professor of Medicine, in the School of Medicine

My laboratory is interested mechanisms of kidney injury in disease states and the role of the kidney in regulation of blood pressure. Our research addresses issues that are relevant to disorders such as hypertension, diabetic nephropathy, transplant rejection, and autoimmune diseases. We have been particularly interested in two hormone systems that impact these processes: (1) the renin-angiotensin system and (2) lipid mediators derived from cyco-oxygenase metabolism of arachidonic acid. Our studies have taken advantage of available technologies for producing genetic alterations in mice to study the physiology of these systems. As one example, we generated and characterized lines of mice lacking the major physiological receptors for angiotensin II in the mouse. These studies have provided novel information regarding the role of these receptors in blood pressure homeostasis, in promoting kidney injury in disease states, and in the regulation of inflammation. A major objective of our work is to identify new approaches to treatment and disease prevention. To this end, we are using molecular genetic technology to develop and refine mouse models of human diseases such as diabetic nephropathy, kidney transplant rejection, and hypertension.

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