Abstract P311: Cardiac Sympathetic Afferents Does Not Initiate but Contributes to the Further Development of Hypertension in Spontaneous Hypertensive Rats

Abstract

Sympatho-excitation plays a critical role in the pathogenesis of hypertension. However, it is unclear what factors initiate and maintain sympatho-excitation in hypertension. Our past studies have confirmed a critical role of cardiac sensory nerve endings that mediate a sympatho-excitatory reflex called the “cardiac sympathetic afferent reflex” (CSAR) in the setting of heart failure. However, whether/when the CSAR is activated and contributes to the development of hypertension remains unclear. To address this issue, we chronically abolished the CSAR by epidural application of a selective afferent neurotoxin, resiniferatoxin (RTX) at the level of the T1-T4 dorsal root ganglia (DRGs) by destroying TRPV1-expressing neuronal soma in 8-week and 16-w old spontaneous hypertensive rats (SHR). Conscious blood pressure was monitored before (baseline) and during 2 months post RTX using radio telemetry. As shown in Figure 1A, in early-hypertensive (8-w old) SHR rats, there was no difference in mean arterial pressure (MAP) between vehicle and RTX groups until 3 weeks post intervention. At that time, MAP in vehicle-treated SHR rats continued to increase whereas this increase was largely abolished in the RTX-treated group. In the established (16-w old) SHR rats (Figure 1B), treatment with RTX immediately reduced MAP by ~15 mmHg, which was maintained for the 2-month recording period. These data strongly suggest that although CSAR does not initiate hypertension at the early stage in SHR, it contributes to the further development of hypertension in the mid/late stages. These data support a potential novel therapy possibly involving cardiac afferents.