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Title page for ETD etd-08052016-101814


Type of Document Dissertation
Author Kraemer, Maria Palazzo
URN etd-08052016-101814
Title Interactions between Angiotensin II and Prostaglandin E2: Mechanisms for Regulation of Vascular Reactivity
Degree PhD
Department Biochemistry
Advisory Committee
Advisor Name Title
John York Committee Chair
Bruce Carter Committee Member
Fred Lamb Committee Member
Jeff Reese Committee Member
Rich Breyer Committee Member
Keywords
  • vascular reactivity
  • blood pressure
  • angiotensin II
  • prostaglandin E2
Date of Defense 2016-08-03
Availability unrestricted
Abstract
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 Ang II potentiated PGE2-evoked constriction in a concentration dependent manner. 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.
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