Prostaglandin F2alpha elevates blood pressure and promotes atherosclerosis.
Little is known about prostaglandin F(2alpha) in cardiovascular homeostasis. Prostaglandin F(2alpha) dose-dependently elevates blood pressure in WT mice via activation of the F prostanoid (FP) receptor. The FP is expressed in preglomerular arterioles, renal collecting ducts, and the hypothalamus. Deletion of the FP reduces blood pressure, coincident with a reduction in plasma renin concentration, angiotensin, and aldosterone, despite a compensatory up-regulation of AT1 receptors and an augmented hypertensive response to infused angiotensin II. Plasma and urinary osmolality are decreased in FP KOs that exhibit mild polyuria and polydipsia. Atherogenesis is retarded by deletion of the FP, despite the absence of detectable receptor expression in aorta or in atherosclerotic lesions in Ldlr KOs. Although vascular TNF(alpha), inducible nitric oxide enzyme and TGF(beta) are reduced and lesional macrophages are depleted in the FP/Ldlr double KOs, this result reflects the reduction in lesion burden, as the FP is not expressed on macrophages and its deletion does not alter macrophage cytokine generation. Blockade of the FP offers an approach to the treatment of hypertension and its attendant systemic vascular disease.
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ying
Y
Yu
Margaret B
MB
Lucitt
Jane
J
Stubbe
Yan
Y
Cheng
Ulla G
UG
Friis
Pernille B
PB
Hansen
Boye L
BL
Jensen
Emer M
EM
Smyth
Garret A
GA
FitzGerald
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D001794:Blood Pressure; D015237:Dinoprost / Q000502:physiology*; D005260:Female; D006973:Hypertension / Q000209:etiology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011982:Receptors, Prostaglandin; D014409:Tumor Necrosis Factor-alpha; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D052247:Nitric Oxide Synthase Type II; D012083:Renin