dc.creator | Kraemer, Maria Palazzo | |
dc.date.accessioned | 2020-08-22T20:43:53Z | |
dc.date.available | 2017-08-05 | |
dc.date.issued | 2016-08-05 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-08052016-101814 | |
dc.identifier.uri | http://hdl.handle.net/1803/13834 | |
dc.description.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. | |
dc.format.mimetype | application/pdf | |
dc.subject | vascular reactivity | |
dc.subject | blood pressure | |
dc.subject | angiotensin II | |
dc.subject | prostaglandin E2 | |
dc.title | Interactions between Angiotensin II and Prostaglandin E2: Mechanisms for Regulation of Vascular Reactivity | |
dc.type | dissertation | |
dc.contributor.committeeMember | Rich Breyer | |
dc.contributor.committeeMember | Bruce Carter | |
dc.contributor.committeeMember | Jeff Reese | |
dc.contributor.committeeMember | Fred Lamb | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Biochemistry | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2017-08-05 | |
local.embargo.lift | 2017-08-05 | |
dc.contributor.committeeChair | John York | |