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

Abstract

PGE2 is a major prostanoid found in the kidney and vasculature contributing to the regulation of blood pressure. The PGE2 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 anti-hypertensive therapy.

VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure

“…We and others have previously reported that the EP1 and EP3 receptors are vasoconstrictors, whereas the EP2 and EP4 receptors are vasodilators, indicating the PGE2/EPs system is essential for blood pressure regulation (3)(4)(5)(6). Increasing evidence also demonstrates that the PGE2/EPs system plays a critical role in vascular remodeling (7,8). EP4 appears to be important for both physiological and pathological vascular remodeling.…”

Intrauterine calorie restriction affects placental DNA methylation and gene expression

“…Ptger1 with its function of regulating blood pressure has also been associated with diabetes, preeclampsia, and premature birth; all three conditions can be associated with IUGR and have long-term fetal programming implications. Ptger1 is also known to mediate hypertension resulting in end organ damage (4).…”

Regulation of arterial reactivity by concurrent signaling through the E-prostanoid receptor 3 and angiotensin receptor 1

“…EP1 receptor knockout mice display a reduced rise in mean arterial blood pressure in response to Ang II infusion and are protected against end-organ damage in hypertensive mouse models [20, 21]. Similarly, EP3 receptor knockout mice have a blunted blood pressure response to acute administration of Ang II [22].…”