Corin, atrial natriuretic peptide and hypertension.
Corin, atrial natriuretic peptide and hypertension.
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DOI：
10.1093/ndt/gfn727
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发表时间：
2008-12
期刊：
影响因子：
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通讯作者：
Yiqing Zhou;Jingjing Jiang;Yujie Cui;Qingyu Wu
中科院分区：
文献类型：
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作者：
Yiqing Zhou;Jingjing Jiang;Yujie Cui;Qingyu Wu
心钠素是从心脏分泌出来的。它与肾脏和血管中的受体结合，促进盐的排泄，降低血容量，放松血管。这种内分泌机制连接心脏和肾脏，维持电解质和体液的良好平衡。ANP通路的生理重要性已在许多动物研究中显示。例如，在小鼠中，ANP缺乏导致高血压[9]，而ANP过度表达导致低血压[10]。ANP基因敲除小鼠的高血压对高盐饮食敏感，表明ANP在体内调节对盐的反应中起关键作用。心脏还产生另一种肽，脑或B型利钠肽（BNP），其具有与ANP相似的利钠和利尿活性。然而，BNP敲除小鼠血压正常，但发生了心脏纤维化[11]，这表明BNP的生理功能可能与ANP不同。在人类中，在ANP基因中发现了几种单核苷酸多态性（SNP）。其中一个（-C664 G）位于启动子区。遗传学研究表明，-664G等位基因与患者的低血浆ANP水平、高血压和左心室肥大相关[12，13]。最近，在一个欧洲血统的家族中报告了ANP基因的移码突变[14]。该突变废除了终止密码子，产生了在ANP的C末端具有12个额外氨基酸的突变分子。这个家族中携带突变基因的成员发生了房颤。其中一些人还患有高血压，需要医疗干预。在动物模型中，突变的ANP显示出缩短心肌细胞的单相动作电位，这可能解释了患者中心房颤动的表型。
sure are increased, ANP is secreted from the heart. It binds to its receptor in the kidney and blood vessels, and promotes salt excretion, lowers blood volume and relaxes the vessel. This endocrine mechanism links the heart and kidney in maintaining a fine balance of electrolytes and body fluid. The physiological importance of the ANP pathway has been shown in many animal studies. In mice, for example,ANPdeficiencycauseshypertension[9],whereasANP overexpression results in hypotension [10]. The hypertension in ANP null mice is sensitive to high dietary salts, indicating that ANP is critical in regulating the response to salt in vivo. The heart also makes another peptide, brain or B-type natriuretic peptide (BNP), which has similar natriuretic and diuretic activity to that of ANP. BNP null mice, however, had normal blood pressure but developed cardiac fibrosis [11], suggesting that the physiological function of BNP may differ from that of ANP. In humans, several single nucleotide polymorphisms (SNPs) have been found in the ANP gene. One of them (-C664G) is located in the promoter region. Genetic studies showed that the -664G allele was associated with low plasma ANP levels, high blood pressure and left ventricular hypertrophy in patients [12,13]. Most recently, a frameshift mutation in the ANP gene was reported in a family of European ancestry [14]. This mutation abolished the stop codon, creating a mutant molecule with 12 extra amino acids at the C-terminus of ANP. The members of this family with the mutant gene developed atrial fibrillation. Some of them also had hypertension that required medical intervention. In an animal model, the mutant ANP was shown to shorten monophasic action potential in cardiomyocytes, which may explain the phenotype of atrial fibrillation in the patients.