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High fat diet increases blood pressure and blunts 2nd‐order baroreceptive neuronal responses to leptin and melanocyte‐stimulating hormone (MSH) in the nucleus tractus solitarius (NTS)

It is well recognized that obesity plays an important role in the increment of blood pressure (BP) and the development of hypertension. The NTS is a pivotal central site integrating gastrointestinal and baroreceptor afferent signals. We previously showed a decreased neuronal excitability of 2nd‐order baroreceptive neurons in NTS in rats fed with high fat diet. Here, we hypothesized that high fat diet decreases leptin and melanocortin signaling in the NTS. Sprague Dawley rats were randomly assigned to a control or high fat diet group (45% cal from fat). Blood pressure was measured with a telemetry transmitter. High fat diet increased body weight by 27%, BP by 18%, and plasma leptin level by 163% compared to age matched rats (p<0.05). Using patch‐clamp techniques, we measured membrane excitability in anatomically identified 2nd‐order baroreceptive neurons with a fluorescent dye applied to the aortic depressor nerve. Leptin (100 nM) induced cell membrane hyperpolarization and reduced input resistance in normal diet group but not in high fat diet group (p<0.05). αMSH (500 nM) depolarized neurons to a greater extent in normal diet group compared to high fat diet group (p<0.05) with no change in input resistance. Data suggest a down regulation of leptin and melanocortin signaling to the 2nd‐order baroreceptive neurons may contribute to obesity‐induced hypertension.