EP1 Disruption Attenuates End-Organ Damage in a Mouse Model of Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2012-11, Vol.60 (5), p.1184-1191
• Main Authors: Bartlett, Christina S, Boyd, Kelli L, Harris, Raymond C, Zent, Roy, Breyer, Richard M
• Format: Article
• Language: English
• Subjects: Angiotensin II; Animals; Antihypertensive Agents - pharmacology; Aortic Aneurysm - genetics; Aortic Aneurysm - physiopathology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - genetics; Blood Pressure - physiology; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Desoxycorticosterone; Disease Models, Animal; Female; Humans; Hydralazine - pharmacology; Hypertension - etiology; Hypertension - genetics; Hypertension - physiopathology; Kaplan-Meier Estimate; Kidney - metabolism; Kidney - pathology; Kidney - physiopathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Nephrectomy; Receptors, Prostaglandin E, EP1 Subtype - deficiency; Receptors, Prostaglandin E, EP1 Subtype - genetics
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.112.199026

Prostaglandin E2 is a major prostanoid found in the kidney and vasculature contributing to the regulation of blood pressure. The prostaglandin E2 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.