Open AccessProstaglandin F 2α elevates blood pressure and promotes atherosclerosis
Author(s) -
Ying Yu,
Margaret B. Lucitt,
Jane Stubbe,
Yan Cheng,
Ulla Glenert Friis,
Pernille Hansen,
Boye L. Jensen,
Emer M. Smyth,
Garret A. FitzGerald
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0811834106
Subject(s) - endocrinology , medicine , angiotensin ii , angiotensin ii receptor type 1 , blood pressure , renin–angiotensin system , prostaglandin , receptor , aldosterone , polyuria , chemistry , diabetes mellitus
Little is known about prostaglandin F2α in cardiovascular homeostasis. Prostaglandin F2α 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 TNFα , inducible nitric oxide enzyme and TGFβ 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.