{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:43:33Z","timestamp":1785840213933,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK67620"],"award-info":[{"award-number":["DK67620"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2212\/\u2212 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\u2212\/\u2212 mice (p &lt; 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1\u2212\/\u2212 mice (p &lt; 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1\u2212\/\u2212 mice on WD (all p &lt; 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1\u03b1, and interleukin-6 in both WT and TRPV1\u2212\/\u2212 mice (all p &lt; 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p &lt; 0.05) but not in TRPV1\u2212\/\u2212 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 &lt; 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1\u2212\/\u2212 mice (all p &lt; 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1\u2212\/\u2212 mice (p &lt; 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.<\/jats:p>","DOI":"10.3390\/cells10051234","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T06:01:33Z","timestamp":1621317693000},"page":"1234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity"],"prefix":"10.3390","volume":"10","author":[{"given":"Beihua","family":"Zhong","sequence":"first","affiliation":[{"name":"Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangtao","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8979","DOI":"10.1038\/s41598-019-45062-w","article-title":"Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice","volume":"9","author":"Sonne","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1161\/hh2001.098351","article-title":"Prostaglandin H synthase and vascular function","volume":"89","author":"Davidge","year":"2001","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1172\/JCI117620","article-title":"Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction","volume":"94","author":"Harris","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1161\/01.CIR.0000124718.99562.91","article-title":"Association of type 2 diabetes with cyclooxygenase-mediated inflammation and oxidative stress in an elderly population","volume":"109","author":"Helmersson","year":"2004","journal-title":"Circulation"},{"key":"ref_5","first-page":"H2316","article-title":"Renal protective effect of chronic inhibition of COX-2 with SC-58236 in streptozotocin-diabetic rats","volume":"300","author":"Quilley","year":"2011","journal-title":"Am. J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000181859","article-title":"Effect of prostacyclin (PGI2) on renal function and renin secretion in hypophysectomized dogs","volume":"25","author":"Gullner","year":"1980","journal-title":"Nephron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1161\/01.HYP.30.3.664","article-title":"Comparative effect of PGE2 and PGI2 on renal function","volume":"30","author":"Villa","year":"1997","journal-title":"Hypertension"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"V38","DOI":"10.1161\/01.HYP.5.6_Pt_3.V38","article-title":"Prostacyclin (PGI2) synthesis in the vascular wall of rats with bilateral renal artery stenosis","volume":"5","author":"Morera","year":"1983","journal-title":"Hypertension"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1161\/01.HYP.0000174603.27383.67","article-title":"Diuresis and natriuresis caused by activation of VR1-positive sensory nerves in renal pelvis of rats","volume":"46","author":"Zhu","year":"2005","journal-title":"Hypertension"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1124\/jpet.108.136374","article-title":"Interdependent regulation of afferent renal nerve activity and renal function: Role of transient receptor potential vanilloid type 1, neurokinin 1, and calcitonin gene-related peptide receptors","volume":"325","author":"Xie","year":"2008","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R1882","DOI":"10.1152\/ajpregu.90529.2008","article-title":"Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity","volume":"295","author":"Kopp","year":"2008","journal-title":"Am. J. Physiol Regul Integr Comp. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1161\/HYPERTENSIONAHA.109.132167","article-title":"Ablation of transient receptor potential vanilloid 1 abolishes endothelin-induced increases in afferent renal nerve activity: Mechanisms and functional significance","volume":"54","author":"Xie","year":"2009","journal-title":"Hypertension"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1161\/HYPERTENSIONAHA.111.185538","article-title":"Tonic postganglionic sympathetic inhibition induced by afferent renal nerves?","volume":"59","author":"Ditting","year":"2012","journal-title":"Hypertension"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1113\/jphysiol.2011.207944","article-title":"Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature","volume":"589","author":"Haddock","year":"2011","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1161\/01.CIR.0000041244.79165.25","article-title":"Sympathetic neural activation in visceral obesity","volume":"106","author":"Alvarez","year":"2002","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1196\/annals.1367.010","article-title":"Sympathetic system activity in obesity and metabolic syndrome","volume":"1083","author":"Tentolouris","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1038\/oby.2007.201","article-title":"Baroreflex sensitivity in obesity: Relationship with cardiac autonomic nervous system activity","volume":"15","author":"Skrapari","year":"2007","journal-title":"Obesity"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1096\/fj.14-268300","article-title":"Transient receptor potential vanilloid type-1 channel regulates diet-induced obesity, insulin resistance, and leptin resistance","volume":"29","author":"Lee","year":"2015","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.1038\/s41598-021-82829-6","article-title":"TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons","volume":"11","author":"Li","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"F1269","DOI":"10.1152\/ajprenal.00230.2004","article-title":"Activation of EP4 receptors contributes to prostaglandin E2-mediated stimulation of renal sensory nerves","volume":"287","author":"Kopp","year":"2004","journal-title":"Am. J. Physiol Renal Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1159\/000107665","article-title":"TRPV1-mediated diuresis and natriuresis induced by hypertonic saline perfusion of the renal pelvis","volume":"27","author":"Zhu","year":"2007","journal-title":"Am. J. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1124\/jpet.109.160473","article-title":"Sensing of blood pressure increase by transient receptor potential vanilloid 1 receptors on baroreceptors","volume":"331","author":"Sun","year":"2009","journal-title":"J. Pharmacol. Exp. Ther.."},{"key":"ref_23","first-page":"F1512","article-title":"Delayed recovery of renal regional blood flow in diabetic mice subjected to acute ischemic kidney injury","volume":"293","author":"Shi","year":"2007","journal-title":"Am. J. Physiol."},{"key":"ref_24","first-page":"407","article-title":"Measurement of regional blood flow in the kidney using laser-Doppler flowmetry","volume":"51","author":"Roman","year":"2001","journal-title":"Methods Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1111\/j.1523-1755.2004.00600.x","article-title":"Utility of endogenous creatinine clearance as a measure of renal function in mice","volume":"65","author":"Dunn","year":"2004","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/oby.2012.4","article-title":"Changes in baroreflex control of renal sympathetic nerve activity in high-fat-fed rats as a predictor of hypertension","volume":"20","author":"Fardin","year":"2012","journal-title":"Obesity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"R858","DOI":"10.1152\/ajpregu.00830.2007","article-title":"Impaired responsiveness of renal sensory nerves in streptozotocin-treated rats and obese Zucker diabetic fatty rats: Role of angiotensin","volume":"294","author":"Kopp","year":"2008","journal-title":"Am. J. Physiol Regul Integr Comp. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.2337\/diacare.24.11.2016-b","article-title":"Acute hyperglycemia and autonomic function","volume":"24","author":"Marfella","year":"2001","journal-title":"Diabetes Care."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s11011-008-9101-x","article-title":"The enhanced hyperglycemic response to hemorrhage hypotension in obese rats is related to an impaired baroreflex","volume":"23","author":"Silveira","year":"2008","journal-title":"Metab. Brain Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1161\/HYPERTENSIONAHA.109.138065","article-title":"Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus","volume":"54","author":"Arnold","year":"2009","journal-title":"Hypertension"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/S0165-1838(96)00074-4","article-title":"Insulin microinjection into the nucleus tractus solitarii of the rat attenuates the baroreceptor reflex","volume":"61","author":"McKernan","year":"1996","journal-title":"J. Auton. Nerv. Syst."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1210\/rp.59.1.225","article-title":"Leptin and the cardiovascular system","volume":"59","author":"Rahmouni","year":"2004","journal-title":"Recent Prog. Horm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1046\/j.1365-2362.2003.01170.x","article-title":"Impaired cardiovagal and vasomotor responses to baroreceptor stimulation in type II diabetes mellitus","volume":"33","author":"Sanya","year":"2003","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1161\/01.HYP.0000169053.14440.7d","article-title":"Diabetic neuropathy is a more important determinant of baroreflex sensitivity than carotid elasticity in type 2 diabetes","volume":"46","author":"Ruiz","year":"2005","journal-title":"Hypertension"},{"key":"ref_35","first-page":"H1113","article-title":"Increase in sympathetic activity with age. I. Role of impairment of arterial baroreflexes","volume":"260","author":"Hajduczok","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/cvr\/cvp084","article-title":"Salicylates dilate blood vessels through inhibiting PYK2-mediated RhoA\/Rho-kinase activation","volume":"83","author":"Ying","year":"2009","journal-title":"Cardiovasc Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/CS20050251","article-title":"Eicosanoids and renal vascular function in diseases","volume":"111","author":"Imig","year":"2006","journal-title":"Clin. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1744-8069-2-26","article-title":"Nociceptors in cardiovascular functions: Complex interplay as a result of cyclooxygenase inhibition","volume":"2","author":"Premkumar","year":"2006","journal-title":"Mol. Pain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.cmet.2010.05.015","article-title":"Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension","volume":"12","author":"Yang","year":"2010","journal-title":"Cell Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1161\/01.HYP.24.2.220","article-title":"Nitric oxide increases renal blood flow by interacting with the sympathetic nervous system","volume":"24","author":"Kumagai","year":"1994","journal-title":"Hypertension"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:03:05Z","timestamp":1760162585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/5\/1234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["cells10051234"],"URL":"https:\/\/doi.org\/10.3390\/cells10051234","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,18]]}}}