Prostaglandin F2α elevates blood pressure and promotes atherosclerosis

被引:87
作者
Yu, Ying [1 ]
Lucitt, Margaret B. [1 ]
Stubbe, Jane [1 ]
Cheng, Yan [1 ]
Friis, Ulla G. [2 ]
Hansen, Pernille B. [2 ]
Jensen, Boye L. [2 ]
Smyth, Emer M. [1 ]
FitzGerald, Garret A. [1 ]
机构
[1] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA
[2] Univ So Denmark, Dept Physiol & Pharmacol, DK-5000 Odense C, Denmark
基金
美国国家卫生研究院;
关键词
hypertension; renin; PGF(2 alpha) receptor; juxtaglomerular granular cell; water metabolism; SMOOTH-MUSCLE-CELLS; ANGIOTENSIN-II; PROSTANOID RECEPTORS; DEFICIENT MICE; RENOVASCULAR HYPERTENSION; JUXTAGLOMERULAR CELLS; RENIN INHIBITION; LIGAND-BINDING; F RECEPTOR; KIDNEY;
D O I
10.1073/pnas.0811834106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Little is known about prostaglandin F-2 alpha in cardiovascular homeostasis. Prostaglandin F-2 alpha 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.
引用
收藏
页码:7985 / 7990
页数:6
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