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  1. Article ; Online: Activation of TRPV1-Expressing Renal Sensory Nerves of Rats with N-Oleoyldopamine Attenuates High-Fat-Diet-Induced Impairment of Renal Function

    Shuang-Quan Yu / Shuangtao Ma / Donna H. Wang

    International Journal of Molecular Sciences, Vol 24, Iss 6207, p

    2023  Volume 6207

    Abstract: Enhanced renal sympathetic nerve activity (RSNA) contributes to obesity-induced renal disease, while the role of afferent renal nerve activity (ARNA) is not fully understood. The present study tested the hypothesis that activating the transient receptor ... ...

    Abstract Enhanced renal sympathetic nerve activity (RSNA) contributes to obesity-induced renal disease, while the role of afferent renal nerve activity (ARNA) is not fully understood. The present study tested the hypothesis that activating the transient receptor potential vanilloid 1 (TRPV1) channel in afferent renal nerves suppresses RSNA and prevents renal dysfunction and hypertension in obese rats. N-oleoyldopamine (OLDA, 1 ng/kg, daily) was administrated intrathecally (T8-L3) via an indwelled catheter to chronically activate, TRPV1-positive afferent renal nerves in rats fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD intake significantly increased the body weight, impaired glucose and insulin tolerance, decreased creatinine clearance, and elevated systolic blood pressure in rats compared with the levels of the chow-fed rats (all p < 0.05). An intrathecal OLDA treatment for 8 weeks did not affect the fasting glucose level, glucose tolerance, and insulin tolerance in rats fed either chow or HFD. As expected, the chronic OLDA treatment significantly increased the levels of plasma calcitonin gene-related peptide and substance P and ARNA in the HFD-fed rats (all p < 0.05). Interestingly, the OLDA treatment decreased the urinary norepinephrine level and RSNA in rats fed HFD (both p < 0.05). Importantly, the OLDA treatment attenuated HFD-induced decreases in creatinine clearance and urinary Na + excretion and increases in the plasma urea level, urinary albumin level, and systolic blood pressure at the end of an 8-week treatment (all p < 0.05). Taken together, the intrathecal administration of OLDA ameliorates the enhancement of RSNA, renal dysfunction, and hypertension in obese rats. These findings shed light on the roles of TRPV1-positive renal afferent nerves in obesity-related renal dysfunction and hypertension.
    Keywords N-oleoyldopamine ; TRPV1 ; high-fat diet ; obesity ; hypertension ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 630
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. 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
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. 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
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Development of salt-sensitive hypertension in a sensory denervated model

    Donna H Wang / Yan Huang

    Journal of the Renin-Angiotensin-Aldosterone System, Vol

    the underlying mechanisms

    2001  Volume 2

    Abstract: We use a novel salt-sensitive hypertensive model recently developed in our laboratory. This model shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with a significant rise in blood pressure (BP) ...

    Abstract We use a novel salt-sensitive hypertensive model recently developed in our laboratory. This model shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with a significant rise in blood pressure (BP). To test the hypothesis that development of salt-sensitive hypertension in sensory denervated rats is mediated by abnormal regulation of both circulating and tissue renin-angiotensin systems (RAS), neonatal Wistar rats were given capsaicin, 50 mg/kg s.c., on the first and second days of life. Control rats were treated with vehicle solution. After the weaning period, male rats were divided into four groups and subjected to the following treatments for three weeks: control + high sodium diet (4%, CON-HS), capsaicin pretreatment + normal sodium diet (0.5%, CAP-NS), capsaicin pretreatment + high sodium diet (CAP-HS), and capsaicin pretreatment + high sodium diet + candesartan cilexetil (10 mg/kg/per day, CAP-HS-CAN). Radioimmunoassay shows that plasma renin activity (ng/ml/hr, PRA) was higher in CAP-NS (2.58±0.17) than in CON-HS (0.14±0.03) and CAP-HS (0.74±0.15), and it was higher in CAP-HS than in CON-HS (p<0.05). Western blot analysis shows that expression of the angiotensin II (Ang II) type 1 (AT1) receptor in both the renal cortex and outer medulla was higher in CAP-HS than in CON-HS and CAP-NS rats (p<0.05). Expression of the Ang II type 2 (AT2) receptor in the renal cortex was higher in both CAP-HS and CAP-NS than in CON-HS rats (p<0.05), but there was no difference in AT2-receptor expression in the renal medulla between CAP-HS, CAP-NS, and CON-HS rats. Likewise, there was no difference in AT1-receptor expression in mesenteric resistance arteries between CAP-HS, CAP-NS, and CON-HS rats. In contrast, mesenteric AT2-receptor expression was lower in CAP-HS than in CAP-NS and CON-HS rats (p<0.05). Tail-cuff systolic BP (mmHg) shows that blockade of the AT1-receptor with candesartan prevents the development of hypertension in CAP-HS rats (by the end of the experiment, CON-HS, 122±3; CAP-NS, 118±10; CAP-HS, 169±9; CAP-HS-CAN, 129±2, p<0.05). Thus, both circulating and tissue RAS in sensory-denervated rats are abnormally regulated in response to a high-salt intake, which may contribute to increased salt sensitivity and account for the effectiveness of candesartan in lowering BP in this model.
    Keywords Medicine (General) ; R5-920
    Subject code 336
    Language English
    Publishing date 2001-03-01T00:00:00Z
    Publisher Hindawi - SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Polycrystalline-Diamond MEMS Biosensors Including Neural Microelectrode-Arrays

    Donna H. Wang / Ho-Yin Chan / Abed Janoudi / Dean M. Aslam / Michael W. Varney

    Biosensors, Vol 1, Iss 3, Pp 118-

    2011  Volume 133

    Abstract: Diamond is a material of interest due to its unique combination of properties, including its chemical inertness and biocompatibility. Polycrystalline diamond (poly-C) has been used in experimental biosensors that utilize electrochemical methods and ... ...

    Abstract Diamond is a material of interest due to its unique combination of properties, including its chemical inertness and biocompatibility. Polycrystalline diamond (poly-C) has been used in experimental biosensors that utilize electrochemical methods and antigen-antibody binding for the detection of biological molecules. Boron-doped poly-C electrodes have been found to be very advantageous for electrochemical applications due to their large potential window, low background current and noise, and low detection limits (as low as 500 fM). The biocompatibility of poly-C is found to be comparable, or superior to, other materials commonly used for implants, such as titanium and 316 stainless steel. We have developed a diamond-based, neural microelectrode-array (MEA), due to the desirability of poly-C as a biosensor. These diamond probes have been used for in vivo electrical recording and in vitro electrochemical detection. Poly-C electrodes have been used for electrical recording of neural activity. In vitro studies indicate that the diamond probe can detect norepinephrine at a 5 nM level. We propose a combination of diamond micro-machining and surface functionalization for manufacturing diamond pathogen-microsensors.
    Keywords biosensors ; diamond ; electrochemistry ; neural probes ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Biotechnology ; TP248.13-248.65
    Subject code 600
    Language English
    Publishing date 2011-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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