Shek E W, Brands M W, Hall J E
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Hypertension. 1998 Jan;31(1 Pt 2):409-14. doi: 10.1161/01.hyp.31.1.409.
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 (I.V.) infusion. After 7 days of control, leptin was infused into the carotid arteries or femoral vein at 0.1 microg/kg/min for 5 days and 1.0 microg/kg/min for 7 days, followed by a 7-day recovery period. The carotid artery and i.v. infusions of leptin at 1 microg/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 i.v. group after 7 days of the 1 microg/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 i.v. group. Heart rate also increased significantly in both groups at 1 microg/kg/min leptin infusion. Fasting blood glucose and insulin levels decreased significantly at 1 microg/kg/min in both the carotid artery group (-10.5% and -82.5%, respectively) and the i.v. 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.
高血压肥胖人群的血浆瘦素浓度会升高，但瘦素是否导致肥胖患者动脉血压升高尚不清楚。在本研究中，我们测试了将瘦素长期升高至与肥胖患者相当的水平是否会导致动脉血压持续升高，以及中枢神经系统（CNS）机制与全身机制的重要性。五只雄性Sprague-Dawley大鼠在腹主动脉和双侧颈动脉植入慢性非阻塞性导管用于中枢神经系统输注，另外五只大鼠在腹主动脉和股静脉植入导管用于静脉内（I.V.）输注。在对照7天后，以0.1微克/千克/分钟的速率向颈动脉或股静脉输注瘦素5天，然后以1.0微克/千克/分钟的速率输注7天，随后是7天的恢复期。以1微克/千克/分钟的速率经颈动脉和静脉输注瘦素显著提高了血浆瘦素水平，分别从1.2±0.4纳克/毫升升至91±5纳克/毫升以及从0.9±0.1纳克/毫升升至94±9纳克/毫升，但低剂量时两组均无显著升高。低剂量时食物摄入量也没有变化，但在以1微克/千克/分钟的速率输注7天后，颈动脉组食物摄入量减少了约65%，静脉组减少了69%。仅在颈动脉组中，低剂量时平均动脉压（MAP）略有升高，但无统计学意义。然而，在较高剂量时，颈动脉组的MAP从86±1毫米汞柱显著升至94±1毫米汞柱，静脉组从87±1毫米汞柱升至93±1毫米汞柱。在以1微克/千克/分钟的速率输注瘦素时，两组的心率也显著增加。在颈动脉组和静脉组中，以1微克/千克/分钟的速率输注时，空腹血糖和胰岛素水平均显著下降（分别为-10.5%和-82.5%，以及-13.6%和-80.4%）。停止输注瘦素后，所有变量均恢复至对照水平。这些结果表明，循环瘦素的长期升高会导致动脉血压和心率持续升高，这与瘦素在肥胖高血压中可能发挥的作用一致。
