Nagase M, Ando K, Katafuchi T, Kato A, Hirose S, Fujita T
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Japan.
Hypertension. 1997 Aug;30(2 Pt 1):177-83. doi: 10.1161/01.hyp.30.2.177.
The natriuretic peptide system is suggested to be involved in the pathogenesis of salt-sensitive hypertension; a recent report indicated that disruption of the atrial natriuretic peptide precursor gene caused salt-sensitive hypertension. However, natriuretic peptide receptor (NPR)-A knockout mice did not show enhanced salt sensitivity of blood pressure. The aim of the present study was to investigate the role of NPR-C, the other receptor for atrial natriuretic peptide, in increased salt sensitivity of blood pressure. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were placed on a 0.3% or 8% NaCl diet for 4 weeks. Blood pressure was elevated by salt loading only in DS rats. RNase protection assay demonstrated that NPR-C transcript level in the kidney was reduced by chronic salt loading in both DR and DS rats, whereas expression of NPR-A and NPR-B was not altered. The reduction of NPR-C mRNA in response to salt loading was enhanced in DS compared with DR rats. In situ hybridization indicated that the salt-induced NPR-C change was attributed mainly to suppressed expression of NPR-C in the podocytes. NPR-C gene expression was regulated by salt loading in a tissue-specific manner; the marked decrease in NPR-C mRNA by salt loading was seen only in the kidney. These data suggest that the exaggerated salt-induced reduction of NPR-C in the kidney of DS rats may play an important role in the pathogenesis of salt hypertension in this animal, possibly related to impaired renal sodium excretion.
利钠肽系统被认为参与盐敏感性高血压的发病机制；最近一份报告指出，心房利钠肽前体基因的破坏会导致盐敏感性高血压。然而，利钠肽受体（NPR）-A基因敲除小鼠并未表现出血压盐敏感性增强。本研究的目的是探讨心房利钠肽的另一种受体NPR-C在血压盐敏感性增加中的作用。将 Dahl 盐敏感（DS）和盐抵抗（DR）大鼠置于 0.3%或 8% NaCl 饮食中 4 周。仅在 DS 大鼠中，盐负荷使血压升高。核糖核酸酶保护试验表明，慢性盐负荷使 DR 和 DS 大鼠肾脏中的 NPR-C 转录水平降低，而 NPR-A 和 NPR-B 的表达未改变。与 DR 大鼠相比，DS 大鼠中盐负荷引起的 NPR-C mRNA 降低更为明显。原位杂交表明，盐诱导的 NPR-C 变化主要归因于足细胞中 NPR-C 表达的抑制。NPR-C 基因表达受盐负荷的组织特异性调节；盐负荷导致的 NPR-C mRNA 显著降低仅在肾脏中出现。这些数据表明，DS 大鼠肾脏中盐诱导的 NPR-C 过度降低可能在该动物盐性高血压的发病机制中起重要作用，可能与肾钠排泄受损有关。
