Prostaglandin F2α elevates blood pressure and promotes atherosclerosis
Prostaglandin F2α elevates blood pressure and promotes atherosclerosis
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DOI：
10.1073/pnas.0811834106
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发表时间：
2009-05-12
影响因子：
11.1
通讯作者：
FitzGerald, Garret A.
中科院分区：
文献类型：
--
作者：
Yu, Ying;Lucitt, Margaret B.;FitzGerald, Garret A.
前列腺素F-2 α在心血管稳态中的作用尚不清楚。前列腺素F-2 α通过激活F前列腺素（FP）受体，剂量依赖性地升高WT小鼠的血压。FP在肾小球前小动脉、肾集管和下丘脑中表达。FP的缺失降低了血压，同时血浆肾素浓度、血管紧张素和醛固酮浓度降低，尽管AT1受体代偿性上调和血管紧张素II输注后高血压反应增强。血浆和尿液渗透压降低的FP KOs表现为轻度多尿和烦渴。尽管在Ldlr KOs的主动脉或动脉粥样硬化病变中没有可检测到的受体表达，但FP的缺失延缓了动脉粥样硬化的发生。虽然在FP/Ldlr双KOs中，血管TNF - α、诱导型一氧化氮酶和TGF（β）减少，病变巨噬细胞减少，但这一结果反映了病变负担的减轻，因为FP不在巨噬细胞上表达，其缺失不会改变巨噬细胞细胞因子的产生。阻断FP提供了一种治疗高血压及其伴随的全身性血管疾病的方法。
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.