title: EP1 disruption attenuates end-organ damage in a mouse model of hypertension.
abstract: Prostaglandin E(2) is a major prostanoid found in the kidney and vasculature contributing to the regulation of blood pressure. The prostaglandin E(2) receptor EP1 has been shown to contribute to hypertension by mediating angiotensin II-dependent vasoconstriction, although its precise role is incompletely characterized. Disruption of the EP1 receptor in C57BL/6J mice reduced the incidence of mortality during severe hypertension induced by uninephrectomy, deoxycorticosterone acetate, and angiotensin II. Mortality was dependent on all components of the model. Death was a result of aortic aneurysm rupture or occurred after development of anasarca, each of which was reduced in EP1-/- mice. Mean arterial pressure was increased in treated EP1+/+ and EP1-/- mice; however, this elevation was significantly lower in EP1-/- mice. Blood pressure reduction via administration of hydralazine phenocopied EP1-/- mice. Thus, reduction in blood pressure by disruption of EP1 reduced incidence of mortality and decreased organ damage, suggesting that EP1 receptor blockade may be a viable target for antihypertensive therapy.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, 1161 21 Ave, Medical Center North # B3214, Nashville, TN 37232-2372, USA.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Bartlett
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001014:Aortic Aneurysm / Q000235:genetics* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000172:deficiency / Q000235:genetics*
chemical_list: D000959:Antihypertensive Agents; C545636:Ptger1 protein, mouse; D058306:Receptors, Prostaglandin E, EP1 Subtype; D000804:Angiotensin II; D006830:Hydralazine; D003900:Desoxycorticosterone