Regulation of arterial reactivity by concurrent signaling through the E-prostanoid receptor 3 and angiotensin receptor 1.

Kraemer MP, Choi H, Reese J, Lamb FS, Breyer RM
Vascul Pharmacol. 2016 84: 47-54

PMID: 27260940 · PMCID: PMC4976016 · DOI:10.1016/j.vph.2016.05.015

Prostaglandin E2 (PGE2), a cyclooxygenase metabolite that generally acts as a systemic vasodepressor, has been shown to have vasopressor effects under certain physiologic conditions. Previous studies have demonstrated that PGE2 receptor signaling modulates angiotensin II (Ang II)-induced hypertension, but the interaction of these two systems in the regulation of vascular reactivity is incompletely characterized. We hypothesized that Ang II, a principal effector of the renin-angiotensin-aldosterone system, potentiates PGE2-mediated vasoconstriction. Here we demonstrate that pre-treatment of arterial rings with 1nM Ang II potentiated PGE2-evoked constriction in a concentration dependent manner (AUC-Ang II 2.778±2.091, AUC+Ang II 22.830±8.560, ***P<0.001). Using genetic deletion models and pharmacological antagonists, we demonstrate that this potentiation effect is mediated via concurrent signaling between the angiotensin II receptor 1 (AT1) and the PGE2 E-prostanoid receptor 3 (EP3) in the mouse femoral artery. EP3 receptor-mediated vasoconstriction is shown to be dependent on extracellular calcium in combination with proline-rich tyrosine kinase 2 (Pyk2) and Rho-kinase. Thus, our findings reveal a novel mechanism through which Ang II and PGE2 regulate peripheral vascular reactivity.

Copyright © 2016 Elsevier Inc. All rights reserved.

MeSH Terms (15)

Angiotensin II Animals Calcium Dinoprostone Dose-Response Relationship, Drug Femoral Artery Focal Adhesion Kinase 2 Male Mice Mice, Inbred C57BL Mice, Knockout Receptor, Angiotensin, Type 1 Receptors, Prostaglandin E, EP3 Subtype rho-Associated Kinases Vasoconstriction

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