Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone.
Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone.
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去甲肾上腺素能机制在γ-黑素细胞刺激激素相对缺乏的大鼠中导致高血压和葡萄糖代谢异常的证据。
DOI：
10.1113/expphysiol.2009.046748
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发表时间：
2009
影响因子：
2.7
通讯作者：
Humphreys,MichaelH
中科院分区：
文献类型：
--
作者：
Ni,Xi-Ping;vanDijk,Claudia;Pearce,David;Humphreys,MichaelH
盐敏感型高血压和胰岛素抵抗之间的密切联系已经被认识到20多年了，尽管这种关系背后的机制(S)还没有被阐明。最近在γ-黑素细胞刺激素(γ-MSH)系统遗传紊乱的小鼠中的数据表明，该系统在高血压和摄入高钠饮食(8%Nacl，HSD)期间糖代谢改变之间的病理生理关系中发挥了作用。我们通过研究多巴胺能激动剂溴隐亭(5 mg kgγ，每天1次，共1周)治疗引起相对的−-msh缺乏症的大鼠，验证了这两种中断γ-msh信号的结果是交感神经激活的结果的假设。喂饲高脂饮食的溴处理组大鼠出现高血压，还表现出空腹高血糖(P<；0.005)和高胰岛素血症(P<；0.025)。此外，在HSD上用溴处理的大鼠糖耐量受损，胰岛素介导的葡萄糖处置迟钝。γ2-MSH或α肾上腺素能受体拮抗剂酚妥拉明静脉滴注15min后，平均动脉压(MAP)和血糖均降至正常(P<；0.0 0 1比对照组)，但对给药和喂饲HSD的大鼠无影响；γ2-MSH在降低MAP和血糖浓度的同时，也可使升高的血浆去甲肾上腺素降至正常水平。给Bromo-HSD大鼠输注肼丙嗪可降低MAP，但对血糖的影响不大。我们的结论是，γ-MSH相对缺乏的大鼠在摄入HSD时会出现糖代谢异常，并具有胰岛素抵抗的特征，与高血压相关。γ2-MSH可使盐敏感型高血压大鼠血浆去甲肾上腺素水平恢复正常，提示盐敏感性高血压与相对γ-MSH缺乏症所致的糖代谢受损可能存在肾上腺素能联系。
A close association between salt‐sensitive hypertension and insulin resistance has been recognized for more than two decades, although the mechanism(s) underlying this relationship have not been elucidated. Recent data in mice with genetic disruption of the γ‐melanocyte‐stimulating hormone (γ‐MSH) system suggest that this system plays a role in the pathophysiological relationship between hypertension and altered glucose metabolism during ingestion of a high‐sodium diet (8% NaCl, HSD). We tested the hypothesis that these two consequences of interrupted γ‐MSH signalling were the result of sympathetic activation by studying rats treated with the dopaminergic agonist bromocriptine (5 mg kg−1i.p.,daily for 1 week; Bromo) to cause relative γ‐MSH deficiency. Bromo‐treated rats fed the HSD developed hypertension and also exhibited fasting hyperglycaemia (P< 0.005) and hyperinsulinaemia (P< 0.025). Furthermore, Bromo‐treated rats on the HSD had impaired glucose tolerance and blunted insulin‐mediated glucose disposal. Intravenous infusion of γ2‐MSH, or of the α‐adrenergic receptor antagonist phentolamine, to Bromo–HSD rats lowered both mean arterial pressure (MAP) and blood glucose to normal after 15 min (P< 0.001versuscontrol), but had no effect in rats receiving vehicle and fed the HSD; γ2‐MSH infusion also reduced the elevated plasma noradrenaline to control levels in parallel with the reductions in MAP and blood glucose concentration. Infusion of hydralazine to Bromo–HSD rats lowered MAP but had only a trivial effect on blood glucose. We conclude that rats with relative γ‐MSH deficiency develop abnormal glucose metabolism, with features of insulin resistance, in association with hypertension when ingesting the HSD. Elevated plasma noradrenaline concentration in Bromo–HSD rats is normalized by γ2‐MSH infusion, suggesting that an adrenergic mechanism may link the salt‐sensitive hypertension and the impaired glucose metabolism of relative γ‐MSH deficiency.