Cardiovascular effects of melanocortins.
Cardiovascular effects of melanocortins.
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DOI：
10.1016/j.ejphar.2010.10.102
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发表时间：
2011-06-11
影响因子：
5
通讯作者：
Pearce, David
中科院分区：
文献类型：
--
作者：
Humphreys, Michael H.;Ni, Xi-Ping;Pearce, David
关键词：
黑皮质素（MSH）是衍生自阿黑皮素原的三种结构相关的肽。它们调节多种生理功能，包括能量代谢、食欲和炎症。最近在啮齿类动物中的研究也确定了MSH，特别是γ-MSH对钠代谢和血压调节的重要作用。正常大鼠和小鼠对高钠饮食的反应是血浆γ-MSH浓度增加，并保持正常血压，而遗传或药理学γ-MSH缺乏的大鼠和小鼠在高钠饮食下会变得高血压。这种高血压通过外源性施用肽来纠正。缺乏γ-MSH受体（黑皮质素3受体，Mc 3r）的小鼠在高钠饮食下也会变得高血压，但当给予γ-MSH时仍然如此，并且生理水平的肽的输注刺激正常大鼠和小鼠的尿钠排泄，但在Mc 3r缺失的小鼠中不刺激尿钠排泄。γ-MSH信号传导受损的啮齿类动物中的盐敏感性高血压似乎是由于去甲肾上腺素能活性的刺激，因为血浆去甲肾上腺素增加，并且高血压通过输注α-肾上腺素受体拮抗剂酚妥拉明迅速纠正。与生理水平的γ-MSH的抗高血压特性相反，静脉内或脑室内注射高水平的该肽会升高血压。这发生在缺乏Mc 3r的小鼠中，表明与其他一些中枢受体的相互作用。最后，啮齿类动物的盐敏感性高血压伴随着γ-MSH信号转导的破坏，并伴有胰岛素抵抗，这一观察结果为研究盐敏感性高血压与胰岛素抵抗和II型糖尿病的关系提供了新的窗口。
Melanocortins (MSH’s) are three structurally related peptides derived from proopiomelanocortin. They regulate several physiologic functions including energy metabolism, appetite, and inflammation. Recent work in rodents has also identified important effects of MSH’s, particularly γ-MSH, on sodium metabolism and blood pressure regulation. Normal rats and mice respond to a high sodium diet with an increase in the plasma concentration of γ-MSH, and remain normotensive, while those with genetic or pharmacologic γ-MSH deficiency become hypertensive on a high sodium diet. This hypertension is corrected by exogenous administration of the peptide. Mice lacking the γ-MSH receptor (the melanocortin 3 receptor, Mc3r) also become hypertensive on a high sodium diet but remain so when administered γ-MSH, and infusions of physiologic levels of the peptide stimulate urinary sodium excretion in normal rats and mice, but not in mice with deletion of Mc3r. The salt-sensitive hypertension in rodents with impaired γ-MSH signaling appears due to stimulation of noradrenergic activity, since plasma noradrenaline is increased and the hypertension is rapidly corrected with infusion of the α-adrenoceptor antagonist phentolamine. In contrast to the antihypertensive property of physiologic levels of γ-MSH, intravenous or intracerebroventircular injections of high levels of the peptide raise blood pressure. This occurs in mice lacking Mc3r, indicating an interaction with some other central receptor. Finally, the salt-sensitive hypertension in rodents with disruption of γ-MSH signaling is accompanied by insulin resistance, an observation which offers a new window into the study of the association of salt-sensitive hypertension with insulin resistance and type II diabetes.
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通讯作者：
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DOI：
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