Abstract

Background: This study tested the hypothesis that genetically ablation of transient receptor potential vanilloid type 1 (TRPV1) exacerbates impairment of baroreflex in mice fed a western diet (WD) and leads to distinct diurnal and nocturnal blood pressure patterns.Methods: TRPV1 gene knockout (TRPV1-/-) and wild-type (WT) mice were given a WD or normal diet (CON) for 4 months.Results: Capsaicin, a selective TRPV1 agonist, increased ipsilateral afferent renal nerve activity in WT but not TRPV1-/- mice. The sensitivity of renal sympathetic nerve activity and heart rate responses to baroreflex were reduced in TRPV1-/--CON and WT-WD and further decreased in TRPV1-/--WD compared to the WT-CON group. Urinary norepinephrine and serum insulin and leptin at day and night were increased in WT-WD and TRPV1-/--WD, with further elevation at night in TRPV1-/--WD. WD intake increased leptin, IL-6, and TNF-α in adipose tissue, and TNF-α antagonist III, R-7050, decreased leptin in TRPV1-/--WD. The urinary albumin level was higher in TRPV1-/--WD than WT-WD. Blood pressure was not dif-ferent during daytime among all groups, but increased at night in the TRPV1-/--WD group compared with other groups.Conclusions: TRPV1 ablation leads to elevated nocturnal but not diurnal blood pressure, which is probably attributed to fur-ther enhancement of sympathetic drives at night.

Highlights

  • Western diet (WD) intake leads to obesity which is linked to hypertension, diabetes, and renal dysfunction [1]

  • Mean arterial pressure (MAP) detected by telemetry was not different at the daytime between all groups but increased at the nighttime in transient receptor potential vanilloid 1 (TRPV1)-/--western diet (WD) compared with WT-CON, TRPV1-/--CON, and WT-WD (P

  • Compared with the CON group, urine NE was significantly increased in WD groups, a further increase was observed in the TRPV1-/--WD group at the nighttime but not in daytime (P

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Summary

Introduction

Western diet (WD) intake leads to obesity which is linked to hypertension, diabetes, and renal dysfunction [1]. Recent studies have demonstrated that obesity is associated with increased sympathetic nerve activity (SNA) in the skeletal muscle and kidney [2, 3]. Baroreflex sensitivity (BRS), which is attenuated whenever sympathetic activity is enhanced [6], is severely impaired in obese subjects [7]. This study tested the hypothesis that genetically ablation of transient receptor potential vanilloid type 1 (TRPV1) exacerbates impairment of baroreflex in mice fed a western diet (WD) and leads to distinct diurnal and nocturnal blood pressure patterns

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