G protein-coupled receptor kinase 4: role in blood pressure regulation.
G protein-coupled receptor kinase 4: role in blood pressure regulation.
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DOI：
10.1161/hypertensionaha.107.096487
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发表时间：
2008
期刊：
影响因子：
8.3
通讯作者：
C. Zeng;V. Villar;G. Eisner;Scott M. Williams;R. Felder;P. Jose
中科院分区：
文献类型：
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作者：
C. Zeng;V. Villar;G. Eisner;Scott M. Williams;R. Felder;P. Jose
近30%的美国中年人患有高血压，但在非西班牙裔黑人和60岁以上的人群中患病率更高（65%）。1高血压值与死亡率之间存在直接的定量关系。虽然30%至50%被认为是遗传的，但原发性高血压的遗传原因一直难以确定。毫无疑问，不止一个基因参与，因为孟德尔显性和隐性性状在高血压受试者中不容易辨别，除了那些单基因形式的高血压。此外，在任何高血压个体中，风险易感基因参与了基因-基因和基因环境相互作用的复杂网络。2、3肾脏在血压的长期调节中起主要作用，高血压时常出现氯化钠代谢异常。因此，许多研究集中在原发性高血压的发病机制中的肾脏对氯化钠的异常处理。2，4大约50%的原发性高血压患者对氯化钠敏感。5事实上，患有盐敏感性高血压的人肾近端小管和髓质粗升支中的钠转运增加，尽管也可能涉及远端小管机制。[6]高血压中的钠潴留是由于钠转运增强本身和/或对降低钠转运的信号未能做出适当反应。钠转运受钠尿和抗钠尿激素以及体液因子（如多巴胺和血管紧张素）的调节，其通过G蛋白偶联受体（GPCR）发挥作用。某些连接后多巴胺受体亚型（D1 R、D3 R、D4 R和D5 R）和血管紧张素2型受体的激活抑制钠转运，而连接后D2 R和血管紧张素1型受体（AT 1 R）的激活增加钠转运。二、七
Nearly 30% of middle-aged Americans have hyperten-sion, but the prevalence is higher in non-Hispanic blacks and individuals 60 years of age (65%). 1 There is a direct and quantitative relationship between higher blood pressure values and mortality. Although 30% to 50% is thought to be heritable, the genetic cause (s) of essential hypertension has been difficult to identify. More than 1 gene is undoubtedly involved, because Mendelian dominant and recessive traits are not readily discernible in hypertensive subjects, except in those with monogenic forms of hypertension. Moreover, in any hypertensive individual, risk-predisposing genes are engaged in a complex network of gene-gene and geneenvironment interactions. 2, 3 The kidney plays a major role in the long-term regulation of blood pressure, and abnormal sodium chloride metabolism is frequently encountered in hypertension. Therefore, many studies have focused on the abnormal renal handling of sodium chloride in the pathogenesis of essential hypertension. 2, 4 Approximately 50% of subjects with essential hypertension are sodium chloride sensitive. 5 Indeed, humans with salt-sensitive hypertension have increased sodium transport in the renal proximal tubule and medullary thick ascending limb, although distal tubular mechanisms may also be involved. 6 The sodium retention in hypertension is because of enhanced sodium transport, per se, and/or a failure to respond appropriately to signals that decrease sodium transport. Sodium transport is regulated by natriuretic and antinatriuretic hormones and humoral agents, such as dopamine and angiotensin, which exert their effects via G protein–coupled receptors (GPCRs). Activation of certain postjunctional dopamine receptor subtypes (D1R, D3R, D4R, and D5R) and the angiotensin type 2 receptor inhibit, whereas activation of the postjunctional D2R and angiotensin type 1 receptor (AT1R) increase sodium transport. 2, 7