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

Abstract

Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. This study tested whether the metabolic and renal effects of SA were mediated by the TRPV1 channel. Wild-type (WT) and TRPV1−/− mice were fed a Western diet (WD) for 4 months and received SA infusion (120mg/kg/day) or vehicle for the last 4 weeks of WD feeding. SA treatment significantly increased blood pressure in WD-fed TRPV1−/− mice (p < 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1−/− mice (p < 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1−/− mice on WD (all p < 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1α, and interleukin-6 in both WT and TRPV1−/− mice (all p < 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p < 0.05) but not in TRPV1−/− mice. Importantly, SA increased serum creatinine and urine kidney injury molecule-1 levels and decreased the glomerular filtration rate in obese WT mice (all p < 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1−/− mice (all p < 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1−/− mice (p < 0.05) but not in WT mice. Taken together, SA-elicited metabolic benefits and anti-inflammatory effects are independent of TRPV1, while SA-induced sympathetic suppression is dependent on TRPV1 channels. SA-induced renal dysfunction is dependent on intact TRPV1 channels. These findings suggest that SA needs to be cautiously used in patients with obesity or diabetes, as SA-induced renal dysfunction may be exacerbated due to impaired TRPV1 in obese and diabetic patients.

Fat-free mass is associated with exercise pressor responses, but not cold pressor responses, in humans: influence of maximal voluntary contraction

“…Regarding the exercise pressor reflex, few studies have directly examined changes in obesity independent of comorbid conditions (such as hypertension or metabolic syndrome). Several studies have examined the role of transient potential receptor potential vanilloid 1 (TRPV1) channels in obesity using knockout models ( 45 – 47 ), and generally indicate that TRPV1 channels differentially contribute to thermogenic and sympathetic regulation in animal models of obesity. However, upon review, no studies have directly examined how potential changes in TRPV1 expression or function contribute to obesity-related changes in exercise pressor reflex activation, nor is there an appreciable body of evidence evaluating obesity related changes in the expression or function of acid-sensing ion channels (ASICs) and/or purinergic receptor contributions to exercise pressor reflex engagement.…”

Neuromechanical Dimorphism of Hypoglycemic Effect of Electroacupuncture

“…C57BL/6 mice were used as wild-type control. The model has been employed extensively in numerous experiments [14, 15]. Every 12 h, the mice’s environment switches from being dark to being light, with a constant temperature of 20–24°C.…”

TRPV1: A promising therapeutic target for skin aging and inflammatory skin diseases

“…TRPV1 is a multimodal nociceptor that is activated and/or allosterically modulated by various thermal, mechanical and chemical stimuli ( Holzer, 2008 ). In addition to capsaicin, the thermal sensitivity of TRPV1 is controlled by other endogenous substances including ATP, bradykinin, nerve growth factor (NGF) ( NatureChuang et al, 2001 ), inflammatory mediators such as arachidonic acid amides ( Sinning et al, 2008 ) and prostaglandin ( Zhong et al, 2021 ). Similarly, TRPV1 also is activated by other exogenous physical or chemical stimuli, such as camphor and resiniferatoxin (RTX), vanillatoxins 1–3 (tarantula), ginger, and ethanol ( Holzer, 2008 ).…”