Elimination of nucleus of the solitary tract (NTS) neurokinin‐1 receptor (NK1R) expressing neurons enhances heart rate adaption and attenuates body weight loss during chronic restraint stress in spontaneously hypertensive rats

Abstract

Chronic stress is associated with cardiovascular hyperreactivity, a risk factor for later cardiovascular disease. Increases in heart rate (HR) and mean arterial pressure (MAP) adapt slowly during daily restraint in the stress sensitive spontaneously hypertensive rat (SHR). Experiments were performed to test the hypothesis that elimination of neurokinin‐1 receptor (NK1R) expressing neurons in the nucleus of the solitary tract (NTS) would enhance adaption of the cardiovascular responses to chronic restraint stress in SHR. The NK1R neurons were ablated by microinjection of the targeted neurotoxin stable substance‐P saporin (SSP) or saporin vehicle (SAP) into the NTS of SHR implanted with telemetry transmitters to measure MAP and HR. Three weeks after NK1R ablation, rats were restrained in a Plexiglas tube for 1 hr/day for 14 d. SSP significantly reduced the increase in HR, but not MAP during daily restraint (p<0.05, 2‐way RM ANOVA). For example, on day 7 the HR area under the curve was 8144±361 (SAP; n=11) vs 6250±260 bpm/60 min (SSP; n=10). SSP treatment also reduced body weight loss during chronic stress. On day 1 after restraint body weight was reduced ‐4.6±1.2 g in SSP vs ‐6.2±1.6 g in SAP rats. By day 14 weight loss was ‐6.0± 4.1 g (SSP) and ‐14.5±2.8 g (SAP). We conclude that in SHR, NTS NK1R neuron ablation enhances adaption of the HR response and attenuates weight loss during chronic restraint stress. (Support: HL‐67183)