Role of γ melanocyte-stimulating hormone-renal melanocortin 3 receptor system in blood pressure regulation in salt-resistant and slat-sensitive rats
Role of γ melanocyte-stimulating hormone-renal melanocortin 3 receptor system in blood pressure regulation in salt-resistant and slat-sensitive rats
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DOI：
10.1016/j.metabol.2009.04.022
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发表时间：
2009-10-01
影响因子：
9.8
通讯作者：
Vaziri, Nosratola D.
中科院分区：
文献类型：
--
作者：
Chandramohan, Gangadarshni;Durham, Nicquanna;Vaziri, Nosratola D.
黑素皮质素3受体（MC3-R）对γ黑色素细胞刺激激素（gamma MSH）具有高亲和力和特异性，gamma MSH是一种参与调节血压（BP）和钠排泄的利钠肽。最近的研究表明，正常大鼠在高盐饮食中MC3-R表达增加，血浆γ - MSH升高，这支持了该系统在钠稳态中的作用。我们假设MC3-R对饮食盐的反应失调可能导致盐潴留和盐敏感性高血压患者血压升高。我们检测了高盐或低盐（0.07%）饲料喂养3周的达尔盐敏感（DSS）和达尔盐抗性（DSR）大鼠肾脏MC3-R表达、血浆γ MSH浓度以及对MC3-R激动剂和拮抗剂的反应。高盐饮食显著增加了DSS组的血压，而DSR组没有。高盐饮食导致DSR大鼠血浆γ - MSH增加5倍，肾脏MC3-R增加2倍。低盐饮食组DSS大鼠血浆γ - MSH和肾脏MC3-R丰度显著升高，高盐饮食组维持不变。MC3-R激动剂黑素素II可显著降低DSR大鼠的血压并提高Na排泄分数，但对高盐饮食的DSS大鼠无显著影响。相比之下，MC3-R拮抗剂SHU9119在两组中均显著升高血压并降低钠排泄分数。因此，这些数据表明，伽马msh -肾MC3-R通路在DSS大鼠中被激活，并且似乎具有生物学功能。(c) 2009爱思唯尔公司版权所有。
Melanocortin 3 receptor (MC3-R) has high affinity and specificity to gamma melanocyte-stimulating hormone (gamma MSH), a natriuretic peptide involved in regulation of blood pressure (BP) and sodium excretion. Recent studies showing increased MC3-R expression and elevated plasma gamma MSH in normal rats fed a high-salt diet Support the role of this system in sodium homeostasis. We hypothesized that dysregulation of MC3-R response to dietary salt may contribute to salt retention and BP elevation in salt-sensitive hypertension. We examined renal MC3-R expression, plasma gamma MSH concentration, and response to MC3-R agonist and antagonist ill Dahl salt-sensitive (DSS) and Dahl salt-resistant (DSR) rats fed high-salt or low-salt (0.07%) diets for 3 weeks. Consumption of high-salt diet significantly increased BP in the DSS but not the DSR group. High-salt diet led to a 5-fold increase in plasma gamma MSH and a 2-fold increase ill renal MC3-R in DSR rats. Plasma gamma MSH and renal MC3-R abundance in DSS rats were maximally elevated on low-salt diet and remained unchanged on high-salt diet. Administration of MC3-R agonist melanotan II significantly lowered BP and raised fractional Na excretion in the DSR but not the DSS rats consuming high-salt diet. In contrast, MC3-R antagonist SHU9119 significantly raised BP and lowered fractional Na excretion in both groups. Thus, the data Suggest that gamma MSH-renal MC3-R pathway is activated and appears to be biologically functional in the DSS rats. (c) 2009 Elsevier Inc. All rights reserved.