Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity

Figures

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  Figure 1. SA treatment-induced hypertension in obese TRPV1−/− mice. Telemetric recording of ambulatory blood pressure (A) and 24-h mean arterial pressure (MAP) (B) in WD-fed WT mice and TRPV1−/− mice treated with or without SA. Differences among groups were performed by two-way ANOVA analysis followed by the Tukey–Kramer multiple comparison test. Values are mean ± SEM; n = 5–6; * p < 0.05 vs. TRPV1−/− mice treated without SA.

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  Figure 2. Effects of SA on glucose tolerance and insulin resistance. Area under the curve (AUC) of the insulin tolerance test (A) and glucose tolerance test (B) in WD-fed WT mice and TRPV1−/− mice treated with or without SA. Plasma insulin (C) and leptin (D) levels of WD-fed WT mice and TRPV1−/− mice treated with or without SA. Differences among groups were performed by two-way ANOVA analysis followed by the Tukey–Kramer multiple comparison test. Values are mean ± SEM; n = 6–7; * p < 0.05 vs. isogenic mice treated without SA; # p < 0.05 vs. WT mice with the same treatment.

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  Figure 3. Effects of SA on autonomic nerve activity. (A) Urinary norepinephrine levels of WD-fed WT mice and TRPV1−/− mice treated with or without SA. (B) Intra-renal pelvic infusion of capsaicin-induced afferent renal nerve activity (ARNA). Differences among groups were performed by two-way ANOVA analysis followed by the Tukey–Kramer multiple comparison test. Values are mean ± SEM; n = 6–7; * p < 0.05 vs. isogenic mice treated without SA; # p < 0.05 vs. WT mice with the same treatment.

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  Figure 4. Effects of SA treatment on baroreflex sensitivity. Baroreflex sensitivity of heart rate (HR) in response to intravenous injection of sodium nitroprusside (50μg/mL) (A) and phenylephrine (125 μg/mL) (B) in WD-fed WT mice and TRPV1−/− mice treated with or without SA. Baroreflex sensitivity of RSNA in response to intravenous injection of sodium nitroprusside (50 μg/mL) (C) and phenylephrine (125 μg/mL) (D) in WD-fed WT mice and TRPV1−/− mice treated with or without SA. Differences among groups were performed by two-way ANOVA analysis followed by the Tukey–Kramer multiple comparison test. Values are mean ± SEM; n = 5–7; * p < 0.05 vs. isogenic mice treated without SA; # p < 0.05 vs. WT mice with the same treatment.

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  Figure 5. Effects of SA on renal blood flow. Peak changes of mean renal cortical blood flow (CBF) (A) and medullary blood flow (MBF) (B) in response to intravenous bolus injections of angiotensin II (Ang II) at doses of 0.5, 2.5, and 12.5 ng/kg in WD-fed WT mice and TRPV1−/− mice treated with or without SA. Differences among groups were performed by two-way ANOVA analysis followed by the Tukey–Kramer multiple comparison test. Values are mean ± SEM; n = 5–7; * p < 0.05 vs. isogenic mice treated without SA; # p < 0.05 vs. WT mice with the same treatment.

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  Figure 6. Effects of SA on renal inflammatory markers. Renal p65 binding activity (A), urine PGE2 (B), PGF1α (C), and IL-6 (D) in WD-fed WT mice and TRPV1−/− mice treated with or without SA. Differences among groups were performed by two-way ANOVA analysis followed by the Tukey–Kramer multiple comparison test. Values are mean ± SEM; n = 5–7; * p < 0.05 vs. isogenic mice treated without SA; # p < 0.05 vs. WT mice with the same treatment.

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  Figure 7. Effects of SA on renal function. GFR (A), serum creatinine (B), urine Kim-1 (C), and urine albumin (D) in WD-fed WT mice and TRPV1−/− mice treated with or without SA. Differences among groups were performed by two-way ANOVA analysis followed by the Tukey–Kramer multiple comparison test. Values are mean ± SEM; n = 5–7; * p < 0.05 vs. isogenic mice treated without SA; # p < 0.05 vs. WT mice with the same treatment.