Hypothalamic melanocortin receptors and chronic regulation of arterial pressure and renal function
Hypothalamic melanocortin receptors and chronic regulation of arterial pressure and renal function
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DOI：
10.1161/01.hyp.0000048194.97428.1a
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发表时间：
2003-03-01
期刊：
影响因子：
8.3
通讯作者：
Hall, JE
中科院分区：
文献类型：
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作者：
Kuo, JJ;Silva, AA;Hall, JE
本研究检查了慢性黑皮质素-3/4受体（MC 3/4-R）激活或抑制期间心血管和肾功能的控制。在Sprague-Dawley大鼠中植入动脉和静脉导管，用于测量24 h/d的平均动脉压（MAP）和心率（HR）以及用于静脉输注，并在侧脑室插管用于慢性脑室内（ICV）输注。在实验1中，在5天的对照期之后，对大鼠施用MC 3/4-R激动剂MTII（n=7，10 ng/h ICV）或0.9%盐水（n=6，ICV）14天，随后是5天的恢复期。在实验2中，在5天的对照期后，大鼠被给予MC 3/4-R拮抗剂SHU-9119（n=7，1 nmol/h ICV）或0.9%盐水溶剂（n=7，ICV），或在SHU-9119输注期间成对喂养（n=5，1 nmol/h ICV）12天，随后是5天的恢复期。MC 4-R激活使食物摄入量从23+/-1降至10+/-2 g/d。尽管存在摄食减少，但MC 3/4-R激活使MAP增加7+/-1 mm Hg。MC 3/4-R抑制12天使摄食量从21+/-1增加到35+/-4 g/d，HR降低53+/-11 bpm，尽管体重显著增加，但MAP没有变化。在成对喂养以防止食物摄入增加的大鼠中，MC 3/4-R抑制进一步降低HR（-87+/-9 bpm），而MAP不变。因此，慢性下丘脑MC 3/4-R激活升高动脉压，尽管减少了食物摄入，而MC 3/4-R抑制导致显著的体重增加而不升高动脉压。这些观察结果与假设一致，即完整的下丘脑MC 3/4-R可能是过度体重增加以升高动脉压所必需的。
This study examined control of cardiovascular and renal function during chronic melanocortin-3/4 receptor (MC3/4-R) activation or inhibition. Arterial and venous catheters were implanted in Sprague-Dawley rats for measurements of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and for intravenous infusions, and the lateral ventricle was cannulated for chronic intracerebroventricular (ICV) infusions. In experiment 1, after a 5-day control period, rats were administered the MC3/4-R agonist MTII (n=7, 10 ng/h ICV) or 0.9% saline (n=6, ICV) for 14 days, followed by a 5-day recovery period. In experiment 2, after a 5-day control period, rats were administered the MC3/4-R antagonist SHU-9119 (n=7, 1 nmol/h ICV) or 0.9% saline vehicle (n=7, ICV), or pair-fed during SHU-9119 infusion (n=5, 1 nmol/h ICV) for 12 days, followed by a 5-day recovery period. MC4-R activation transiently decreased food intake from 23+/-1 to 10+/-2 g/d. Despite the hypophagia, MC3/4-R activation increased MAP by 7+/-1 mm Hg. MC3/4-R inhibition for 12 days increased food intake from 21+/-1 to 35+/-4 g/d, decreased HR by 53+/-11 bpm, and caused no change in MAP despite the marked weight gain. In rats that were pair-fed to prevent increased food intake, MC3/4-R inhibition further decreased HR (-87+/-9 bpm), whereas MAP was unchanged. Thus, chronic hypothalamic MC3/4-R activation raises arterial pressure despite decreased food intake, whereas MC3/4-R inhibition causes marked weight gain without raising arterial pressure. These observations are consistent with the hypothesis that an intact hypothalamic MC3/4-R may be necessary for excess weight gain to raise arterial pressure.