Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats
Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats
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DOI：
10.2337/diabetes.46.12.2040
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发表时间：
1997-12-01
期刊：
影响因子：
7.7
通讯作者：
Lu, HQ
中科院分区：
文献类型：
--
作者：
Dunbar, JC;Hu, YG;Lu, HQ
肥胖和高胰岛素血症是脂肪组织产生瘦素的主要刺激因素，导致循环中瘦素水平升高。研究还表明，瘦素的增加可能通过降低中枢神经系统（CNS）中神经肽Y （NPY）的水平而导致饱腹感。由于肥胖和高胰岛素血症也经常与高血压相关，我们研究了脑室内（ICV）给药瘦素对平均动脉压（MAP）、心率、血管流量以及腰肾交感神经活动（SNA）的影响。正常Wistar大鼠植入ICV套管，并允许其恢复。在研究当天，动物禁食并用氯氯蔗糖/氨基甲酸乙酯麻醉。在股动脉和股静脉内放置导管，在髂动脉、肾动脉和肠系膜上动脉周围放置多普勒血流探头，测量MAP、心率和血流量。在其他实验中，记录腰椎SNA和肾脏SNA。ICV给药导致MAP缓慢，但；逐步增加。髂动脉和肠系膜上动脉的血流量减少，但肾动脉的血流量没有减少。瘦素注射增加腰椎SNA和肾脏SNA。血糖和胰岛素水平没有变化。我的结论是，ICV瘦素通过减少流向骨骼肌和内脏血管床的动脉血流量而增加MAP。这种外周阻力的增加是交感神经活动增加的结果。我们认为，瘦素升高可能是肥胖、高胰岛素血症和高血压三者之间的联系。
Obesity and hyperinsulinism are known to be major stimuli of leptin production by adipose tissue, leading to increased leptin levels in the circulation. It has also been demonstrated that increased leptin production leads to satiety, possibly by decreasing the levels of neuropeptide Y (NPY) in the central nervous system (CNS). Because obesity and hyperinsulinism are also frequently associated with hypertension, we studied the effect of the intracerebroventricular (ICV) administration of leptin on mean arterial pressure (MAP), heart rate, vascular flows, and lumbar and renal sympathetic nerve activity (SNA). Normal Wistar rats were implanted with an ICV cannula and allowed to recover. On the day of the study, the animals were fasted and anesthetized with chloralose/urethane. Catheters were placed in a femoral artery and vein, and Doppler flow probes were placed around the iliac, renal, and superior mesenteric arteries for measurement of MAP, heart rate, and blood flows. In other experiments, lumbar SNA and renal SNA were recorded. ICV leptin administration resulted in an MAP that was slowly but; progressively increasing. Blood flows decreased in the iliac and superior mesenteric arteries, but not in the renal artery. Leptin injection increased the lumbar SNA and renal SNA. The plasma glucose and insulin levels were not changed. me concluded that ICV leptin increases MAP by decreasing arterial blood flow to the skeletal muscle and the splanchnic vascular bed. This increased peripheral resistance is the result of an increased activity of the sympathetic nerves. We suggest that increased leptin may serve as a link in the triad of obesity and hyperinsulinism and hypertension.