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


CONCLUSIONS
Vascular mPGES-1 acts as an important tonic vasodilator, contributing to acute blood pressure regulation.
Zhang
Dong-juan
DJ
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Chen
Li-hong
LH
Zhang
Ya-hua
YH
Yang
Guang-rui
GR
Dou
Dou
D
Gao
Yuan-sheng
YS
Zhang
Xiao-yan
XY
Kong
Xiao-mu
XM
Zhao
Pan
P
Pu
Dan
D
Wei
Ming-fen
MF
Breyer
Matthew-D
MD
Guan
You-fei
YF
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000652:urine; D013314:Stress, Mechanical; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012964:Sodium; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone