INTRACEREBROVENTRICULAR LEPTIN INCREASES LUMBAR AND RENAL SYMPATHETIC-NERVE ACTIVITY AND BLOOD-PRESSURE IN NORMAL RATS

Obesity and hyperinsulinism are known to be major stimuli of leptin pr oduction by adipose tissue, leading to increased leptin levels in the circulation. It has also been demonstrated that increased leptin produ ction leads to satiety, possibly by decreasing the levels of neuropept ide Y (NPY) in the central nervous system (CNS). Because obesity and h yperinsulinism are also frequently associated with hypertension, we st udied the effect of the intracerebroventricular (ICV) administration o f leptin on mean arterial pressure (MAP), heart rate, vascular flows, and lumbar and renal sympathetic nerve activity (SNA). Normal Wistar r ats were implanted with an ICV cannula and allowed to recover. On the day of the study, the animals were fasted and anesthetized with chlora lose/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 flo ws. In other experiments, lumbar SNA and renal SNA were recorded. ICV leptin administration resulted in an MAP that was slowly but; progress ively increasing. Blood flows decreased in the iliac and superior mese nteric arteries, but not in the renal artery. Leptin injection increas ed the lumbar SNA and renal SNA. The plasma glucose and insulin levels were not changed. me concluded that ICV leptin increases MAP by decre asing arterial blood flow to the skeletal muscle and the splanchnic va scular bed. This increased peripheral resistance is the result of an i ncreased activity of the sympathetic nerves. We suggest that increased leptin may serve as a link in the triad of obesity and hyperinsulinis m and hypertension.