Chronic leptin infusion increases arterial pressure
Chronic leptin infusion increases arterial pressure
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DOI：
10.1161/01.hyp.31.1.409
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发表时间：
1998-01-01
期刊：
影响因子：
8.3
通讯作者：
Hall, JE
中科院分区：
文献类型：
--
作者：
Shek, EW;Brands, MW;Hall, JE
高血压肥胖者血浆瘦素浓度升高，但瘦素是否导致肥胖患者动脉压升高尚不清楚。在这项研究中，我们测试了瘦素的长期增加是否会导致动脉压的持续增加，以及中枢神经系统(CNS)相对于全身机制的重要性。5只雄性SD大鼠在腹主动脉和双侧颈动脉置入慢性非闭塞导管进行中枢神经系统输注，另5只大鼠分别置入腹主动脉导管和股静脉导管进行静脉输注。对照组7d后，颈动脉或股静脉分别注入瘦素0.1mg/kg/min，5d和1.0mg/kg/min，连续7d，7d为恢复期。颈动脉和静脉滴注1 mU g/kg/min瘦素后，血浆瘦素水平明显升高，分别从1.2+/-0.4 ng/m l和0.9+/-0.1 ng/m l增加到91+/-5 ng/m l和94+/-9 ng/m L，但两组在低剂量时均无明显升高。食物摄入量在低剂量下也没有改变，但在1微克/公斤/分钟输注7天后，颈动脉组和静脉组的摄食量分别减少了约65%和69%。平均动脉压(MAP)在低剂量时仅在颈动脉组略有升高，但没有统计学意义。但在高剂量时，颈动脉组的MAP从86+/-1 mm Hg升至94+/-1 mm Hg，静脉注射组的MAP从87+/-1 mm Hg升至93+/-1 mm Hg。输注瘦素1微克/公斤/分钟时，两组的心率也显著增加。空腹血糖和胰岛素水平在1mUg/kg/min时，颈动脉组(分别为-10.5%和-82.5%)和静脉组(分别为-13.6%和-80.4%)均显著降低。停止输注瘦素后，所有变量均恢复到对照水平。这些结果表明，循环中瘦素的慢性增加会导致动脉压和心率的持续增加，这与瘦素在肥胖性高血压中的可能作用是一致的。
Plasma leptin concentration is increased in hypertensive obese humans, but whether leptin contributes to the increased arterial pressure in obesity is not known. In this study, we tested whether chronic increases in leptin, to levels comparable to those in obesity, could cause a sustained increase in arterial pressure and also the importance of central nervous system (CNS) versus systemic mechanisms. Five male Sprague-Dawley rats were implanted with chronic nonoccluding catheters in the abdominal aorta and both carotid arteries for CNS infusion, and five other rats were implanted with an abdominal aorta catheter and femoral vein catheter for intravenous (IV) infusion. After 7 days of control, leptin was infused into the carotid arteries or femoral vein at 0.1 mu g/kg/min for 5 days and 1.0 mu g/kg/min for 7 days, followed by a 7-day recovery period. The carotid artery and IV infusions of leptin at 1 mu g/kg/min significantly increased plasma leptin levels, from 1.2+/-0.4 ng/mL to 91+/-5 ng/ml, and from 0.9+/-0.1 ng/mL to 94+/-9 ng/mL, respectively, but there was no significant increase in either group at the low dose. Food intake also did not change at the low dose but decreased by approximately 65% in the carotid group and 69% in the IV group after 7 days of the 1 mu g/kg/min infusion. Mean arterial pressure (MAP) increased slightly at the low dose only in the carotid group, but this was not statistically significant. At the higher dose, however, MAP increased significantly from 86+/-1 mm Hg to 94+/-1 mm Hg in the carotid group and from 87+/-1 mm Hg to 93+/-1 mm Hg in the IV group. Heart rate also increased significantly in both groups at 1 mu g/kg/min leptin infusion. Fasting blood glucose and insulin levels decreased significantly at 1 mu g/kg/min in both the carotid artery group (-10.5% and -82.5%, respectively) and the IV group (-13.6% and -80.4%, respectively). All variables returned to control levels after leptin infusion was stopped. These results indicate that chronic increases in circulating leptin cause sustained increases in arterial pressure and heart rate and are consistent with a possible role for leptin in obesity hypertension.