Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1

Aim: To examine the contribution of vascular membrane-associated prostaglandin E2 synthase-1 (mPGES-1) to acute blood pressure homeostasis. Methods: Angiotensin II (AngII, 75 pmolkg¹ min¹) was continuously infused via the jugular vein into wild-type and mPGES-1 ^-/- mice for 30 min, and blood pressure was measured by carotid arterial catheterization. RT-PCR and immunohistochemistry were performed to detect the expression and localization of mPGES-1 in the mouse arterial vessels. Mesenteric arteries were dissected from mice of both genotypes to study vessel tension and measure vascular PGE2 levels. Results: Wild-type and mPGES-1 ^-/- mice showed similar blood pressure levels at baseline, and the acute intravenous infusion of AngII caused a greater increase in mean arterial pressure in the mPGES-1 / group, with a similar diuretic and natriuretic response in both groups. mPGES-1 was constitutively expressed in the aortic and mesenteric arteries and vascular smooth muscle cells of wild-type mice. Strong staining was detected in the smooth muscle layer of arterial vessels. Ex vivo treatment of mesenteric arteries with AngII produced more vasodilatory PGE2 in wild-type than in mPGES-1 ^-/- mice. In vitro tension assays further revealed that the mesenteric arteries of mPGES-1 ^-/- mice exhibited a greater vasopressor response to AngII than those arteries of wild-type mice. Conclusion: Vascular mPGES-1 acts as an important tonic vasodilator, contributing to acute blood pressure regulation.