Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1
Abstract
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 pmol·kg−1·min−1) 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.
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Methods: Angiotensin II (AngII, 75 pmol·kg−1·min−1) 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.