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

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. (Hypertension. 2012; 60: 1184-1191.). Online Data Supplement