CHRONIC LEPTIN INFUSION INCREASES ARTERIAL-PRESSURE

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 increas es in leptin, to levels comparable to those in obesity, could cause a sustained increase in arterial pressure and also the importance of cen tral nervous system (CNS) versus systemic mechanisms. Five male Spragu e-Dawley rats were implanted with chronic nonoccluding catheters in th e abdominal aorta and both carotid arteries for CNS infusion, and five other rats were implanted with an abdominal aorta catheter and femora l 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 a t the low dose. Food intake also did not change at the low dose but de creased by approximately 65% in the carotid group and 69% in the IV gr oup 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, b ut 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/mi n 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%, respe ctively). All variables returned to control levels after leptin infusi on was stopped. These results indicate that chronic increases in circu lating leptin cause sustained increases in arterial pressure and heart rate and are consistent with a possible role for leptin in obesity hy pertension.