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Article ; Online: Activation of TRPV1 improves natriuresis and salt sensitivity in high-fat diet fed mice.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

2022 Volume 203, Page(s) 115190

Abstract: Western diet (WD) intake increases morbidity of obesity and salt-sensitive hypertension albeit mechanisms are largely unknown. We investigated the role of transient receptor potential vanilloid 1 (TRPV1) in WD intake-induced hypertension. ... ...

Abstract	Western diet (WD) intake increases morbidity of obesity and salt-sensitive hypertension albeit mechanisms are largely unknown. We investigated the role of transient receptor potential vanilloid 1 (TRPV1) in WD intake-induced hypertension. TRPV1
MeSH term(s)	Animals ; Diet, High-Fat ; Hypertension ; Mice ; Mice, Knockout ; NG-Nitroarginine Methyl Ester/pharmacology ; Natriuresis ; Sodium ; Sodium Chloride ; TRPV Cation Channels/genetics
Chemical Substances	TRPV Cation Channels ; TRPV1 protein, mouse ; Sodium Chloride (451W47IQ8X) ; Sodium (9NEZ333N27) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X)
Language	English
Publishing date	2022-07-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2022.115190
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Article ; Online: Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity

Beihua Zhong / Shuangtao Ma / Donna H. Wang

Cells, Vol 10, Iss 1234, p

2021 Volume 1234

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 ... ...

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.
Keywords	TRPV1 ; obesity ; sodium salicylate ; afferent renal nerve activity ; renal dysfunction ; blood pressure ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

Cells

2021 Volume 10, Issue 5

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
MeSH term(s)	Animals ; Baroreflex/drug effects ; Cyclooxygenase Inhibitors/toxicity ; Diet, High-Fat ; Disease Models, Animal ; Energy Metabolism/drug effects ; Gene Deletion ; Glomerular Filtration Rate/drug effects ; Hemodynamics/drug effects ; Inflammation Mediators/metabolism ; Insulin Resistance ; Kidney/drug effects ; Kidney/innervation ; Kidney/metabolism ; Kidney Diseases/chemically induced ; Kidney Diseases/metabolism ; Kidney Diseases/physiopathology ; Kidney Diseases/prevention & control ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications ; Obesity/drug therapy ; Obesity/metabolism ; Obesity/physiopathology ; Sodium Salicylate/toxicity ; Sympathetic Nervous System/drug effects ; Sympathetic Nervous System/metabolism ; Sympathetic Nervous System/physiopathology ; TRPV Cation Channels/deficiency ; TRPV Cation Channels/genetics ; Mice
Chemical Substances	Cyclooxygenase Inhibitors ; Inflammation Mediators ; TRPV Cation Channels ; TRPV1 protein, mouse ; Sodium Salicylate (WIQ1H85SYP)
Language	English
Publishing date	2021-05-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10051234
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Article ; Online: Knockout of TRPV1 Exacerbates Ischemia-reperfusion-induced Renal Inflammation and Injury in Obese Mice.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

In vivo (Athens, Greece)

2020 Volume 34, Issue 5, Page(s) 2259–2268

Abstract: Background/aim: Transient receptor potential vanilloid type 1 (TRPV1) has anti-inflammatory properties. The present study aimed to investigate the role of TRPV1 in renal inflammatory responses and tissue injury following renal ischemia-reperfusion (I/R) ...

Abstract	Background/aim: Transient receptor potential vanilloid type 1 (TRPV1) has anti-inflammatory properties. The present study aimed to investigate the role of TRPV1 in renal inflammatory responses and tissue injury following renal ischemia-reperfusion (I/R) in diet-induced obese mice. Materials and methods: TRPV1 knockout and wild type mice were fed a normal or western diet (WD) for 23 weeks and were then subjected to renal I/R injury. Results: TRPV1 knockout mice showed enhanced WD-induced renal macrophage infiltration and collagen deposition. Knocking out TRPV1 exacerbated renal I/R-induced increase of malondialdehyde, interleukin-6, monocyte chemoattractant protein-1, and NF-ĸB in obese mice. Similar results were observed in the expression of phosphorylated Smad1 and Smad2/3. Blockade of calcitonin gene-related peptide (CGRP) receptors with CGRP8-37 worsened the I/R-induced renal inflammation and injury. Conclusion: Our data indicate that preserving TRPV1 expression and function may prevent renal I/R injury in obesity likely through alleviating inflammatory responses.
MeSH term(s)	Animals ; Inflammation/genetics ; Ischemia ; Mice ; Mice, Knockout ; Mice, Obese ; Reperfusion ; Reperfusion Injury/complications ; Reperfusion Injury/genetics ; TRPV Cation Channels/genetics
Chemical Substances	TRPV Cation Channels ; TRPV1 protein, mouse
Language	English
Publishing date	2020-08-29
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.12036
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Zs.A 2288: Show issues

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Article: TRPV1 protects renal ischemia-reperfusion injury in diet-induced obese mice by enhancing CGRP release and increasing renal blood flow.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

PeerJ

2019 Volume 7, Page(s) e6505

Abstract: Background: Obesity is a major risk factor for end-stage renal disease. Using transient receptor potential vanilloid 1 knockout (TRPV1: Methods: TRPV1: Results: The Western diet significantly increased body weight and fasting blood glucose levels ... ...

Abstract	Background: Obesity is a major risk factor for end-stage renal disease. Using transient receptor potential vanilloid 1 knockout (TRPV1 Methods: TRPV1 Results: The Western diet significantly increased body weight and fasting blood glucose levels in both TRPV1 Conclusion: These results indicate that TRPV1 plays a protective role in WD-induced exacerbation of renal I/R injury probably through enhancing CGRP release and increasing renal blood flow.
Language	English
Publishing date	2019-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.6505
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Article: Protease-activated receptor 2 protects against myocardial ischemia-reperfusion injury through the lipoxygenase pathway and TRPV1 channels.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

Experimental and therapeutic medicine

2019 Volume 18, Issue 5, Page(s) 3636–3642

Abstract: This study tests the hypothesis that the lipoxygenase (LOX) pathway mediates protease-activated receptor (PAR) 2-induced activation of the transient receptor potential vanilloid receptor 1 (TRPV1) to protect the heart from ischemia/reperfusion (I/R) ... ...

Abstract	This study tests the hypothesis that the lipoxygenase (LOX) pathway mediates protease-activated receptor (PAR) 2-induced activation of the transient receptor potential vanilloid receptor 1 (TRPV1) to protect the heart from ischemia/reperfusion (I/R) injury. SLIGRL, a PAR2 activating peptide, was administered prior to reperfusion following left anterior descending coronary artery ligation in wild type (WT) and TRPV1 knockout (TRPV1
Language	English
Publishing date	2019-09-09
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2019.7987
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Article ; Online: TRPV1 Mediates Glucose-induced Insulin Secretion Through Releasing Neuropeptides.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

In vivo (Athens, Greece)

2019 Volume 33, Issue 5, Page(s) 1431–1437

Abstract: Background/aim: Transient receptor potential vanilloid 1 (TRPV1)-expressing sensory nerves innervate the pancreatic islets. Sensory neuropeptides, including calcitonin gene-related peptide (CGRP) and substance P (SP), participate in insulin secretion. ... ...

Abstract	Background/aim: Transient receptor potential vanilloid 1 (TRPV1)-expressing sensory nerves innervate the pancreatic islets. Sensory neuropeptides, including calcitonin gene-related peptide (CGRP) and substance P (SP), participate in insulin secretion. This study aimed to investigate the role of TRPV1 in glucose-induced insulin secretion. Materials and methods: TRPV1 Results: TRPV1 Conclusion: TRPV1 mediates glucose-induced insulin secretion likely through CGRP and SP release.
MeSH term(s)	Animals ; Glucose/metabolism ; Glucose Intolerance ; Insulin Secretion ; Male ; Mice ; Mice, Knockout ; Neuropeptides/metabolism ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism
Chemical Substances	Neuropeptides ; TRPV Cation Channels ; TRPV1 receptor ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2019-08-27
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.11621
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Zs.A 2288: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: TRPV1 protects renal ischemia-reperfusion injury in diet-induced obese mice by enhancing CGRP release and increasing renal blood flow

Beihua Zhong / Shuangtao Ma / Donna H. Wang

PeerJ, Vol 7, p e

2019 Volume 6505

Abstract: Background Obesity is a major risk factor for end-stage renal disease. Using transient receptor potential vanilloid 1 knockout (TRPV1−/−) mice, we tested the hypothesis that TRPV1 protects against obesity-induced exacerbation of renal ischemia- ... ...

Abstract	Background Obesity is a major risk factor for end-stage renal disease. Using transient receptor potential vanilloid 1 knockout (TRPV1−/−) mice, we tested the hypothesis that TRPV1 protects against obesity-induced exacerbation of renal ischemia-reperfusion (I/R) injury. Methods TRPV1−/− and wild-type (WT) mice were fed a chow or Western diet (WD) for 22–23 weeks. After that, mice were subjected to renal I/R injury, and renal cortical blood flow (CBF) and medullary blood flow (MBF) were measured. Results The Western diet significantly increased body weight and fasting blood glucose levels in both TRPV1−/− and WT mice. WD-induced impairment of glucose tolerance was worsened in TRPV1−/− mice compared with WT mice. WD intake prolonged the time required to reach peak reperfusion in the cortex and medulla (both P < 0.05), decreased the recovery rate of CBF (P < 0.05) and MBF (P < 0.05), and increased blood urea nitrogen, plasma creatinine, and urinary 8-isoprostane levels after I/R in both mouse strains, with greater effects in TRPV1−/− mice (all P < 0.05). Renal I/R increased calcitonin gene-related peptide (CGRP) release in WT but not in TRPV1−/− mice, and WD attenuated CGRP release in WT mice. Moreover, blockade of CGRP receptors impaired renal regional blood flow and renal function in renal I/R injured WT mice. Conclusion These results indicate that TRPV1 plays a protective role in WD-induced exacerbation of renal I/R injury probably through enhancing CGRP release and increasing renal blood flow.
Keywords	TRPV1 ; Renal ischemia-reperfusion ; Renal blood flow ; Western diet ; Calcitonin gene-related peptide ; Medicine ; R ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
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Article ; Online: Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury is Blunted by Diet-Induced Obesity.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

Cardiovascular & hematological disorders drug targets

2019 Volume 20, Issue 2, Page(s) 122–130

Abstract: Background: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed ... ...

Abstract	Background: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study the cardioprotective effects of TRPV1 in obesity. Methods: TRPV1 gene knockout (TRPV1-/-) and Wild-Type (WT) mice were Fed a High-Fat Diet (HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo. The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) and reperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 μmol/L) and SP (0.1 μmol/L). Then, Coronary Flow (CF), left ventricular peak positive dP/dt (+dP/dt), Left Ventricular Developed Pressure (LVDP) and Left Ventricular End-Diastolic Pressure (LVEDP) were measured. Results: HFD intake remarkably reduced CF, +dP/dt and LVDP and elevated LVEDP in both strains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt and LVDP, and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups. Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05). In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/- mice were improved by CGRP and SP. Conclusion: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced impairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/- mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.
MeSH term(s)	Animals ; Blood Glucose/metabolism ; Capsaicin/pharmacology ; Diet, High-Fat ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardial Reperfusion Injury/genetics ; Myocardial Reperfusion Injury/metabolism ; Obesity/metabolism ; TRPV Cation Channels/agonists ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism
Chemical Substances	Blood Glucose ; TRPV Cation Channels ; TRPV1 protein, mouse ; Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2019-09-11
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2244164-5
ISSN	2212-4063 ; 1871-529X
ISSN (online)	2212-4063
ISSN	1871-529X
DOI	10.2174/1871529X19666190912152041
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Zs.A 5610: Show issues

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Article ; Online: Ablation of TRPV1 Elevates Nocturnal Blood Pressure in Western Diet-fed Mice.

Zhong, Beihua / Ma, Shuangtao / Wang, Donna H

Current hypertension reviews

2018 Volume 15, Issue 2, Page(s) 144–153

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 ... ...

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 different 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 further enhancement of sympathetic drives at night.
MeSH term(s)	Animals ; Blood Pressure/physiology ; Circadian Rhythm/physiology ; Cycloleucine/analogs & derivatives ; Cycloleucine/pharmacology ; Diet, Western/adverse effects ; Disease Models, Animal ; Gene Expression Regulation ; Hypertension/drug therapy ; Hypertension/genetics ; Hypertension/metabolism ; Male ; Mice ; Mice, Knockout ; Sympathetic Nervous System/drug effects ; Sympathetic Nervous System/physiopathology ; TRPV Cation Channels/antagonists & inhibitors ; TRPV Cation Channels/biosynthesis ; TRPV Cation Channels/genetics
Chemical Substances	TRPV Cation Channels ; TRPV1 protein, mouse ; Cycloleucine (0TQU7668EI) ; cispentacin (3814-46-8)
Language	English
Publishing date	2018-10-31
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1875-6506
ISSN (online)	1875-6506
DOI	10.2174/1573402114666181031141840
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