Background: Feeding a high fat diet (HFD) to rabbits results in rapidly increased blood pressure (BP), heart rate (HR) and renal sympathetic activity (RSNA) as well as marked increases in plasma leptin and insulin. We determined the central contribution of insulin and leptin signalling in the CNS to the increase MAP, heart rate (HR) and RSNA following a HFD using specific antagonists.
Methods: New Zealand rabbits were implanted with an intracerebroventricular (ICV) catheter and a RSNA electrode and placed on a normal or a 13.5 % HFD for 1 or 3 weeks. At week 1 and 3 of diet, rabbits were administered a leptin antagonist (100 µg ICV), insulin antagonist (0.5U ICV) or Ringer’s.
Results: Rabbits had higher MAP, HR, RSNA, plasma insulin and leptin at 1 and 3 weeks of a HFD compared to controls (n=6-8). ICV Insulin antagonist reduced MAP and HR but not RSNA at week 1 and week 3 of a HFD (P<0.05). There was no effect of leptin antagonist on MAP, HR and RSNA at 1 week HFD, but at 3 weeks the leptin antagonist produced a marked hypotension and reduction in RSNA (P<0.0001). The leptin and insulin antagonist doses were confirmed in separate animals to effectively block the pressor responses to ICV leptin and insulin respectively.
Conclusion: The elevation of MAP and RSNA induced by several weeks of a HFD is predominantly mediated by central sympatho-excitatory actions of leptin. Central actions of insulin contributes a smaller proportion of the hypertension, independently of the RSNA but is responsible for all of the tachycardia due to feeding a HFD.
Disclosure: No conflict of interest