Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat.
Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat.
复制标题
大鼠中，γ-黑素细胞刺激激素分泌的抑制伴随着盐敏感性高血压。
DOI：
10.1161/01.hyp.0000097601.83235.f8
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Humphreys,MichaelH
中科院分区：
文献类型：
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作者：
Mayan,Haim;Ni,Xi-Ping;Almog,Shlomo;Humphreys,MichaelH
γ-促黑素细胞激素（γ-MSH）是垂体神经中间叶（NIL）中阿黑皮素原（POMC）衍生的一种利钠肽;与低钠饮食（LSD; 0.07%）相比，大鼠摄入高钠（HSD; 8% NaCl）后其血浆浓度增加一倍。由于NIL功能是通过多巴胺能途径调节的，因此我们询问是否用溴隐亭（每天5 mg/kg IP，持续1周）刺激多巴胺能或用氟哌啶醇（5 mg/kg IP，持续1周）抑制多巴胺能改变γ-MSH对HSD的反应。在溶剂处理的大鼠中，HSD的血浆γ-MSH和NIL γ-MSH含量均显著高于LSD的值（P<0.001）;平均动脉压（MAP）无差异。在LSD时氟哌啶醇处理的大鼠中，血浆γ-MSH和NIL γ-MSH含量均高于溶剂处理的大鼠（P<0.05），并且在HSD时没有进一步增加; MAP也没有差异。溴隐亭处理组大鼠HSD时血浆γ-MSH和NIL-γ-MSH含量均未增加，HSD时MAP显著升高（132±3 mmHg对106±3 mmHg，P<0.001）。静脉输注γ-MSH（0.4pmol/min）可使血浆γ-MSH浓度恢复到HSD时的水平，MAP由131±6降至108±5 mmHg（P<0.01）。这些结果表明，多巴胺能抑制NIL功能可阻止正常摄入HSD期间NIL含量和γ-MSH血浆浓度的增加。这导致HSD上的γ-MSH缺乏，并伴有血压升高，这通过输注肽来纠正。γ-MSH可能是对HSD正常反应的重要组成部分;这种反应的中断导致盐敏感性高血压。
γ-Melanocyte–stimulating hormone (γ-MSH) is a natriuretic peptide derived from proopiomelanocortin (POMC) in the pituitary neurointermediate lobe (NIL); its plasma concentration in rats doubles after ingestion of a high (HSD; 8% NaCl) compared with a low sodium diet (LSD; 0.07%). Because NIL function is regulated through dopaminergic pathways, we asked whether dopaminergic stimulation with bromocriptine (5 mg/kg IP daily for 1 week) or inhibition with haloperidol (5 mg/kg IP for 1 week) alters the γ-MSH response to a HSD. In vehicle-treated rats, plasma γ-MSH and NIL γ-MSH content on the HSD were both markedly elevated over values in rats on the LSD (P<0.001); no difference in mean arterial pressure (MAP) occurred. In haloperidol-treated rats on the LSD, both plasma γ-MSH and NIL γ-MSH content were greater than in vehicle-treated rats (P<0.05) and did not increase further on the HSD; MAP was also no different. In bromocriptine-treated rats, neither plasma γ-MSH nor NIL γ-MSH content increased on the HSD versus LSD, and MAP was markedly elevated on the HSD (132±3 versus 106±3 mm Hg,P<0.001). Intravenous infusion of γ-MSH (0.4 pmol/min) to bromocriptine-treated rats on the HSD restored plasma γ-MSH concentration to a level appropriate for the HSD and lowered MAP from 131±6 to 108±5 mm Hg (P<0.01). These results demonstrate that the increases in NIL content and plasma concentration of γ-MSH normally occurring during ingestion of the HSD are prevented by dopaminergic suppression of NIL function. This results in deficiency of γ-MSH on the HSD and is accompanied by elevated blood pressure, which is corrected by infusion of the peptide. γ-MSH may be an important component in the normal response to a HSD; interruption of this response leads to salt-sensitive hypertension.