Abstract 042: Carotid Body Ablation of TRPV1 Reduces Chemoreflex Sensitivity in Rats With Heart Failure

Abstract

Resiniferatoxin (RTX), an ultrapotent analogue of capsaicin, activates and destroys TRPV1 expressing cells. RTX in the CB may reduce abnormal breathing patterns seen in rats with HF. The purpose of this study was to examine whether TRPV1 ablation in the CB of HF rats alters chemoreflex-evoked ventilation and cardiovascular function. We used the post-MI model of HF in male SD rats (200-250g). BP (radiotelemetry), cardiac function (echocardiography) and ventilation (plethysmography measured under hypoxic (10% and 15% of O2) and hypercapnic (5% and 7% of CO2) conditions) before and 4 weeks after application of vehicle or RTX (50ug/ml) to the CB. After 4 weeks of MI, the rats showed ejection fraction of 35.9±1.6% demonstrating HF condition. Immunofluorescence showed lower expression of TRPV1 in RTX treated comparing to vehicle-treated CBs. RTX treatment (n=4) reduced baseline MAP (Veh=93.3±2.3 vs RTX=87.1±1.4, p<0.001) and HR (Veh=335.8±10.5 vs RTX=297±10.2, p<0.001) and normalized the increased ventilatory response to hypoxia or hypercapnia in HF rats (Figure). Poincare analyses showed an increase in the breath-breath variability 4 weeks after treatment with veh (SD1=95.9±14.3 vs 198.2±31.9; SD2=135.3±20.2 vs 279.9±45.1), which was blunt by RTX (SD1=87.5±17.7 vs 97.2±23.6; SD2=123.4±25 vs 137.1±33.4; p<0.05). No changes in BP, HR and body temperature were observed during hypoxia and hypercapnia in CHF rats, treated or not with RTX. These data show that CB RTX treatment in HF rats reduces chemoreflex sensitivity. These data implicate an enhanced role for TRPV1 signaling in chemoreflex function in HF.