Abstract 471: Trpv1 Ablation Leads to Elevated Blood Pressure at Night but Not Day Time in Mice Fed a Western Diet

Abstract

Obesity is associated with an increase in renal sympathetic nerve activity (RSNA) and impairment in baroreflex (BR) that raises cardiovascular morbidity and mortality. This study tests the hypothesis that ablation of the transient receptor potential vanilloid type 1 (TRPV1) channels exacerbates impairment of BR in mice fed a western diet (WD) and leads to distinct diurnal and nocturnal blood pressure patterns. TRPV1-null mutant (TRPV1 -/- ) or wild type (WT) mice were given a WD (42% kcal from fat) or normal diet (CON) for 4 months. Perfusion of capsaicin (CAP, 10 -6 M ), a selective TRPV1 agonist, into the left renal pelvis increased ipsilateral afferent renal nerve activity (ARNA) in WT but not TRPV1 -/- mice, with a smaller magnitude in WT-WD compared to WT-CON (P<0.05). The sensitivity of RSNA and heart rate (HR) responses to BR was assessed during changes in mean arterial pressure (MAP) induced by IV infusion of sodium nitroprusside (SNP)- or phenylephrine (PE). The sensitivity of RSNA and HR responses to BR was reduced to the same degree in TRPV1-/-CON and WT-WD and further decreased in TRPV1-/-WD (SNP infusion-RSNA: WT-CON183 ±37.7; TRPV1-/-CON 114.5 ± 15.3; WT-WD 92.1 ± 33.3; TRPV1-/-WD 53.9 ± 26.6%; P<0.05; SNP infusion-HR: WT-CON 47.4 ± 7.6; TRPV1-/-CON 38.6 ± 5.3; WT-WD 36.6 ± 3.0; TRPV1-/-WD 28.2 ± 3.9 beats/min; P<0.05; PE infusion-RSNA: WT-CON -93.9 ±6.4; TRPV1-/-CON -74.3 ± 9.2; WT-WD -66.1 ± 9.0; TRPV1-/-WD -40.6 ± 10.2%; P<0.05; PE infusion-HR: WT-CON -35.5 ± 6.5; TRPV1-/-CON -29.0 ± 3.2.; WT-WD -27.6± 2.9; TRPV1-/-WD -20.2± 3.3 beats/min; P<0.05). Urinary norepinephrine levels at day and night times were increased in WT-WD and TRPV1-/-WD, with further elevated levels at night time in TRPV1-/-WD ( P <0.05). Urinary albumin and plasma creatinine levels were increased in WT-WD and TRPV1-/-WD, with further elevated urinary albumin levels in TRPV1-/-WD ( P <0.05). Telemetry MAP was not different at the day time between all groups, but increased at the night time in TRPV1-/-WD compared to WT-CON, TRPV1-/-CON, and WT-WD (P<0.05). Thus, TRPV1 ablation exacerbates impairment of BR and BR control of RSNA in the face of WD intake, and leads to elevated nocturnal but not diurnal blood pressure possibly attributed to further enhanced sympathetic drives at night time.