Obesity-related hypertension and the role of insulin and leptin in high-fat-fed rabbits

Feeding a high-fat diet (HFD) to rabbits results in increased blood pressure and renal sympathetic nerve activity (RSNA) and marked increases in plasma leptin and insulin. We determined the contribution of insulin and leptin signaling in the central nervous system to the increased blood pressure and RSNA during a HFD using specific antagonists. New Zealand White rabbits were implanted with an intracerebroventricular (ICV) catheter and RSNA electrode and placed on a normal or 13.5 HFD for 1 or 3 weeks. Blood pressure, heart rate, and RSNA were recorded before and for 90 minutes after ICV administration of a leptin antagonist (100 microg), insulin antagonist (0.5 U), or vehicle (50 microL) on separate days. Rabbits had higher blood pressure (+8 , +17 ) and RSNA (+55 , +71 ), at 1 and 3 weeks, respectively, of HFD compared with controls (n=7-11). ICV leptin antagonist reduced blood pressure by 9 and RSNA by 17 (P