Adenosine A2A receptors in the rostral ventrolateral medulla participate in blood pressure decrease with electroacupuncture in hypertensive rats.

Acupuncture is increasingly used to manage high blood pressure (BP) as a complementary therapy. However, the mechanisms underlying its hypotensive effects remain unclear. Our previous studies have shown that electroacupuncture (EA) at the ST36-37 acupoints, overlying the deep peroneal nerve, attenuates pressor responses through adenosine A2A receptors (A2AR) in the rostral ventrolateral medulla (rVLM). However, it is uncertain whether rVLM A2AR contributes to EA's BP-lowering effect in sustained hypertension. We hypothesized that a course of EA treatment lowers BP, in part, through the activation of adenosine A2AR in the rVLM in hypertensive rats. To mimic essential hypertension in the clinic, we performed EA in conscious Dahl salt-sensitive hypertensive rats (DSHRs). EA (0.1-0.4 mA, 2 Hz) was applied at ST36-37 for 30 min twice weekly for four weeks, while sham-EA was conducted in a similar manner but without electrical input. In hypertensive rats, BP was reduced by EA (n = 14) but neither by sham-EA (n = 14) nor in the absence of needling (n = 8). Following four weeks of eight treatments and then under anesthesia, EA's modulatory effect on elevated BP was reversed by unilateral rVLM microinjection of SCH 58261 (1 mM in 50 nl; an A2AR antagonist; n = 7; P < 0.05) but not the vehicle (n = 5) in EA-treated DSHRs. Activation of rVLM A2AR in DSHRs treated with sham-EA by an A2AR agonist, CGS-21680 (0.4 mM in 50 nl; n = 8), decreased BP. Unilateral administration of SCH 58261 or CGS-21680 into the rVLM did not alter basal BP in Dahl salt-sensitive rats fed a regular diet with normal BP. The A2AR level in the rVLM after EA was increased compared to the sham-EA and untreated DSHRs (n = 5 in each group; all P < 0.05). These data suggest that a 4-week twice weekly EA treatment reduced BP in salt-sensitive hypertensive rats likely through adenosine-mediated A2AR in the rVLM.

ShenQiWan ameliorates renal injury in type 2 diabetic mice by modulating mitochondrial fusion and endoplasmic reticulum stress.

Background: ShenQiWan is commonly used in traditional Chinese medicine for the treatment of diabetic nephropathy, which is closely related to mitochondrial fusion and endoplasmic reticulum stress. This study aimed to investigate the intervention effect and molecular mechanisms of ShenQiWan on renal injury in KKAy mice. Methods: C57BL/6J mice (11 weeks old) were fed a regular diet upon arrival, while KKAy mice (11 weeks old) were fed a high-fat diet upon arrival. At 12 weeks of age, KKAy mice with random blood glucose ≥13.9 mmol/L were identified as diabetic mice and randomly divided into the model group (n = 30) and the treatment group (n = 30), while C57BL/6J mice of 12 weeks old (n = 30) served as the control group. The treatment group received daily aqueous decoction of ShenQiWan (13.5 g/kg), while the control group and model group received daily equal amounts of saline from 12 weeks old to 24 weeks old. The general status of mice was observed regularly, and fasting blood glucose and 24-hour urine microalbumin were measured. Ten mice were euthanized in each group at the age of 16, 20, and 24 weeks, serum samples were used for biochemical indexes and kidney tissues were used for morphological studies. GRP78, OPA1, MFN1, MFN2 mRNA and protein expression were detected by Real-time PCR, immunohistochemistry and Western blot. Results: The mice in the model group exhibited symptoms of lethargy, slow movement, obesity, polyuria and proteinuria. Morphological observation revealed pathological changes, including thickening of the glomerular basement membrane and interstitial fibrosis. After treatment with ShenQiWan, the fasting blood glucose level of KKAy mice was significantly reduced, urinary albuminuria was decreased, serum biochemical indexes were improved, renal tissue pathological changes were significantly alleviated. The results also showed a significant reduction in the expression of endoplasmic reticulum stress-related factor GRP78 and an increase in the expression of mitochondrial fusion-related factors OPA1, MFN1 and MFN2 after treatment with ShenQiWan. Conclusion: ShenQiWan can protect diabetic mice from renal damage by modulating mitochondrial fusion and alleviating endoplasmic reticulum stress, exerting its protective effects.

Sympathoinhibitory electroacupuncture (EA) interacts positively with anti-inflammatory EA alleviating blood pressure in hypertensive rats.

Elevated sympathetic activity and chronic inflammation are known contributory factors observed in hypertension. We have observed that sympathoinhibitory electroacupuncture (SI-EA) at acupoints ST36-37 alleviates sympathetic activity and hypertension. Additionally, EA at acupoints SP6-7 exerts anti-inflammatory (AI-EA) effects. However, it is not known whether simultaneous stimulation of this combination of acupoints attenuates or enhances individual effects. A 2 × 2 factorial design was used to test the hypothesis that combining SI-EA and AI-EA (cEA) leads to greater reduction of hypertension by decreasing sympathetic activity and inflammation in hypertensive rats than either set of acupoints alone. Dahl salt-sensitive hypertensive (DSSH) rats were treated with four EA regimens including cEA, SI-EA, AI-EA, and sham-EA twice weekly for five weeks. A group of normotensive (NTN) rats served as control. Systolic and diastolic BP (SBP and DBP) and heart rate (HR) were measured non-invasively by tail-cuff. Plasma norepinephrine (NE), high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) concentrations were determined with ELISA at the completion of treatments. DSSH rats on high salt diet progressively developed moderate hypertension within five weeks. DSSH rats treated with sham-EA showed continuous increase in SBP and DBP and elevations in plasma NE, hs-CRP, and IL-6 levels relative to NTN control. Both SI-EA and cEA decreased SBP and DBP, and had corresponding changes in biomarkers (NE, hs-CRP, and IL-6) compared with sham-EA. AI-EA prevented SBP and DBP elevation and decreased IL-6 and hs-CRP relative to sham-EA. Importantly in DSSH rats that received repetitive cEA treatment, SI-EA interacted positively with AI-EA leading to greater reduction of SBP, DBP, NE, hs-CRP, and IL-6 than SI-EA or AI-EA alone. These data suggest that by targeting both elevated sympathetic activity and chronic inflammation, cEA regimen results in a greater reduction of BP effects in treating hypertension compared to using individual SI-EA or AI-EA alone.

Case report: Significant relief of linezolid-induced peripheral neuropathy in a pre-XDR-TB case after acupuncture treatment.

The revised WHO guidelines on multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) include linezolid in the core drug group. Common adverse events of prolonged linezolid use are bone marrow suppression and peripheral neuropathy (PN). Available measures against linezolid-induced PN (LIPN) often have insignificant effects, leading to linezolid discontinuation and a decline in the success rate of MDR/RR-TB treatment. Acupuncture treatment is a symptomatic treatment measure from traditional Chinese medicine (TCM) to relieve pain with overall very low evidence and has never been reported in LIPN. The pilot use of acupuncture in a pre-extensively drug-resistant (XDR)-TB (a more severe form of MDR/RR-TB) patient exhibited significant improvements in LIPN and thus maintained linezolid in the regimen for a longer period.

Neurogenic Hypotension and Bradycardia Modulated by Electroacupuncture in Hypothalamic Paraventricular Nucleus.

Electroacupuncture (EA) stimulates somatic median afferents underlying P5-6 acupoints and modulates parasympathoexcitatory reflex responses through central processing in the brainstem. Although decreases in blood pressure and heart rate by the neural-mediated Bezold-Jarisch reflex responses are modulated by EA through opioid actions in the nucleus tractus solitarius and nucleus ambiguus, the role of the hypothalamus is unclear. The hypothalamic paraventricular nucleus (PVN) is activated by sympathetic afferents and regulates sympathetic outflow and sympathoexcitatory cardiovascular responses. In addition, the PVN is activated by vagal afferents, but little is known about its regulation of cardiopulmonary inhibitory hemodynamic responses. We hypothesized that the PVN participates in the Bezold-Jarisch reflex responses and EA inhibits these cardiopulmonary responses through the PVN opioid system. Rats were anesthetized and ventilated, and their heart rate and blood pressures were monitored. Application of phenylbiguanide every 10 min close to the right atrium induced consistent depressor and bradycardia reflex responses. Unilateral microinjection of the depolarization blockade agent kainic acid or glutamate receptor antagonist kynurenic acid in the PVN reduced these reflex responses. In at least 70% of the rats, 30 min of bilateral EA at P5-6 acupoints reduced the depressor and bradycardia responses for at least 60 min. Blockade of the CCK-1 receptors converted the non-responders into EA-responders. Unilateral PVN-microinjection with naloxone reversed the EA inhibition. Vagal-evoked activity of the PVN cardiovascular neurons was reduced by 30 min EA (P5-6) through opioid receptor activation. These data indicate that PVN processes inhibitory cardiopulmonary reflexes and participates in EA-modulation of the neural-mediated vasodepression and bradycardia.

Evaluation of the Chemical Composition and Antioxidant Activity of Mulberry (Morus alba L.) Fruits from Different Varieties in China.

Mulberry (Morus alba L.) fruit is a fruit with nutritional and medicinal value. It is widely cultivated in different regions of China, which may result in differences in its chemical composition. In this research, 25 mulberry fruit samples from six provinces in China were investigated. The contents of anthocyanins were evaluated by high-performance liquid chromatography (HPLC). The contents of two main anthocyanins, cyanidin-3-O-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R), ranged from 0.656 ± 0.006 mg/g to 4.367 ± 0.243 mg/g and from 0.226 ± 0.007 mg/g to 1.649 ± 0.013 mg/g, respectively. Additionally, the contents of total phenolic, total flavonoid, vitamin C, titratable acids, reducing sugars and antioxidant capacity (FRAP, DPPH, scavenging and hydroxyl radical scavenging activity) were also assessed. The results and principal component analysis showed that the Zhongsang 5801 variety from Sichuan, Dechang had the greatest health value with the highest active compound contents. Based on our analysis, the variety from Sichuan, Dechang is a high-quality plant source for mulberry fruit cultivation. This research provides a basis for the rational development and utilization of mulberry fruit resources in China.

Two novel aporphine-derived alkaloids from the stems of Fissistigma glaucescens.

Two novel aporphine-derived alkaloids, aporaloids A and B (1 and 2), together with eight known biogenetically related alkaloids (3-10), two known isoquinoline alkaloids (3 and 4), and six known aporphinoid alkaloids (5-10) were isolated from the stems of Fissistigma glaucescens. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 1 and 2 represent the rare example of a six-membered lactone ring aporphine-derived alkaloids from natural products. The inhibitory activities of all compounds against four cancer cell lines were evaluated. Aporaloids A and B (1 and 2) showed broad spectrum cytotoxic activities.

Icariin contributes to healing skull defects in rabbit model.

OBJECTIVE: To investigate the efficacy of icariin for healing skull defects in rabbit models. METHODS: Thirty-six 3-month-old female New Zealand white rabbits, weighing 1.8-2.0 kg each, were randomly divided into either the control or experimental group. Skull defect models were constructed in both groups, with the experimental group receiving oral icariin afterwards. At 4, 8 and 12 postoperative weeks, the rabbits were euthanized, and X-rays and samples were taken. Tissue sections were stained using hematoxylin and eosin, followed by additional processing using histological and bone metrological methods for observing the rate and quality of the bone formation. RESULTS: Histologically, additional mature lamellar bone formed in the defect area in the experimental group compared with that of the control group. Bone metrological methods showed that the bone mass, trabecular bone width and number of osteoblasts in the experimental group were significantly higher than those of the control group (P < 0.01). The number of osteoclasts did not significantly differ between the two groups (P > 0.05). CONCLUSION: Icariin increased the bone mass and improved the condition of the defect area in the rabbit skulls.

Determination of the Non-metallic Elements in Herbal Tea by Inductively Coupled Plasma Tandem Mass Spectrometry.

The feasibility of using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) to overcome spectral overlaps in the determination of non-metallic elements was investigated. The contents of Si, P, S, Cl, Br, and I in herbal tea were determined by using ICP-MS/MS after microwave digestion. In the MS/MS mode, O2 and H2 were consecutively used as reaction gases. Low background equivalent concentration (BEC) and limit of detection (LOD) of analytes were obtained when using O2 mass shift, H2 mass shift, and H2 on-mass methods. The LODs for Si, P, S, Cl, Br, and I were 0.41, 0.048, 0.34, 0.76, 0.055, and 0.007 µg L-1, respectively. Standard reference materials NIST SRM 1515 (apple leaves) and NIST SRM 1547 (peach leaves) were used to evaluate the accuracy of the analytical method. The developed method was used to analyze 20 herbal teas. The ranges of values for Si, P, S, Cl, Br, and I in herbal tea were 236-4100, 1830-4360, 1290-3850, 335-4620, 0.86-8.21, and 0.091-0.65 µg g-1, respectively. The results showed that several non-metallic elements essential for the human body might be obtained by drinking herbal tea.

Unconventional ferroelectricity in moiré heterostructures.

The constituent particles of matter can arrange themselves in various ways, giving rise to emergent phenomena that can be surprisingly rich and often cannot be understood by studying only the individual constituents. Discovering and understanding the emergence of such phenomena in quantum materials-especially those in which multiple degrees of freedom or energy scales are delicately balanced-is of fundamental interest to condensed-matter research1,2. Here we report on the surprising observation of emergent ferroelectricity in graphene-based moiré heterostructures. Ferroelectric materials show electrically switchable electric dipoles, which are usually formed by spatial separation between the average centres of positive and negative charge within the unit cell. On this basis, it is difficult to imagine graphene-a material composed of only carbon atoms-exhibiting ferroelectricity3. However, in this work we realize switchable ferroelectricity in Bernal-stacked bilayer graphene sandwiched between two hexagonal boron nitride layers. By introducing a moiré superlattice potential (via aligning bilayer graphene with the top and/or bottom boron nitride crystals), we observe prominent and robust hysteretic behaviour of the graphene resistance with an externally applied out-of-plane displacement field. Our systematic transport measurements reveal a rich and striking response as a function of displacement field and electron filling, and beyond the framework of conventional ferroelectrics. We further directly probe the ferroelectric polarization through a non-local monolayer graphene sensor. Our results suggest an unconventional, odd-parity electronic ordering in the bilayer graphene/boron nitride moiré system. This emergent moiré ferroelectricity may enable ultrafast, programmable and atomically thin carbon-based memory devices.

Chinese Propolis Inhibits the Proliferation of Human Gastric Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest.

Special Chinese propolis sourced from the Changbai Mountains (CBMP) in Northeast China is rich in specific flavonoids and phenolic acids and its bioactivity has not been reported. This study aimed to investigate the antiproliferative effect of CBMP on cancer cells and its molecular mechanisms. Different cancer cell lines were treated with the ethanol extracts of CBMP for 24 hours before the cell viability and mechanism measurements. The results showed CBMP had weak activities against human pancreatic cancer cell PANC1, human lung cancer cell A549, human colon cancer cell HCT116, human liver cancer cell HepG2, human bladder cancer cell T24, and human breast cancer cell MDA-MB-231, but it significantly inhibited the growth of human gastric cancer SGC-7901 cells, caused cell apoptosis and cell cycle arrest in S phase, with increased production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential (MMP). The results indicate that Chinese propolis sourced from the Changbai Mountains selectively inhibits the proliferation of human gastric cancer SGC-7901 cells by inducing both death receptor-induced apoptosis and mitochondria-mediated apoptosis, and cell cycle arrest in S phase. These activities and mechanisms help understand the anticancer action of propolis and its active compounds.

Phosphorus supply via a fed-batch strategy improves lipid heterotrophic production of Chlorella regularis.

Intracellular phosphorus (P) accumulation can improve microalgal growth and lipid synthesis. However, large excess of P causes cell poisoning. This study utilized a P-fed-batch strategy to investigate its potential to improve the utilization of the excessive P, while avoiding toxic side effects. This strategy contributed to a more complete utilization of the intracellularly stored P, which enhanced the microalgae biomass by 10-15% by upregulating the brassinosteroid growth hormone gene at a P-fed-batch frequency of 2-8. Furthermore, the lipid content increased by 4-16% via upregulation of lipid synthesis-related genes. As a result, the P-fed-batch strategy significantly increased the lipid production by 13-19%. The content of saturated fatty acid increased by ~ 100%, implying improved combustibility and oxidative stability. This is the first study of this P-fed-batch strategy and provides a new concept for the complete utilization of excessive P.

Royal jelly attenuates nonalcoholic fatty liver disease by inhibiting oxidative stress and regulating the expression of circadian genes in ovariectomized rats.

Nonalcoholic fatty liver disease (NAFLD) has a high incidence in postmenopausal women and is accompanied by insulin resistance, obesity, and dyslipidemia. Royal jelly (RJ), a natural substance derived from hive, possesses numerous health-beneficial properties. Here, we evaluated the effects of RJ (150, 300, and 450 mg kg-1  day-1 , 8 weeks) on NAFLD in ovariectomized (OVX) rats. Based on the results, RJ ameliorated the degree of anxiety, improved serum lipid profile, and attenuated the hepatic steatosis and liver injury in OVX rats. Furthermore, the protective effects of RJ could be attributed to its antioxidant properties, which enhance the levels of hepatic antioxidant enzymes. The qRT-PCR results also suggest that RJ improves the disturbances of circadian genes by downregulating their expression, including that of Per1 and Per 2, in the liver of OVX rats. Altogether, our findings suggest that RJ may be a promising agent for the treatment of NAFLD. PRACTICAL APPLICATIONS: Postmenopausal women are at an increased risk of NAFLD. Currently, there are no licensed therapies for NAFLD. Although hormone replacement therapy (HRT) is reported to inhibit the development of NAFLD, it causes unexpected adverse effects. As HRT is controversial, the use of natural supplements to counteract the detrimental effects of menopause has recently attracted more attention. RJ is a natural product secreted from the hypopharyngeal and mandibular glands of worker bees. The present study illustrates the protective effect of the natural product, RJ, and its underlying mechanisms on NAFLD. This is the first study to assess the effect of RJ on NAFLD under estrogen deficiency. Such findings contribute to the further utilization of RJ, which might serve as a promising therapeutic option and natural food for the treatment of NAFLD.

Effect of ultrasonic treatment combined with 1-methylcyclopropene (1-MCP) on storage quality and ethylene receptors gene expression in harvested apple fruit.

The objective of our study was to investigate the effectiveness of ultrasonic treatment combined with 1-methylcyclopropene (1-MCP) on storage quality and gene expression of postharvest apples compared with ultrasonic or 1-MCP treatment alone. Ethylene production, respiratory rate, firmness, soluble solid content (SSC), peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) activity, and ethylene receptors gene expression of apples were tested. The results indicated 1-MCP or ultrasonic treatment-restrained ethylene production and respiratory rate, improved firmness, suppressed the escalation of SSC, enhanced the activities of POD, SOD, and CAT, suppressed the gene expression level of MdETR1 and MdERS1 compared with the untreated samples. Furthermore, effect of the combination was more observable than that of ultrasonic or 1-MCP alone. In a word, the results proved the technology of ultrasonic plus 1-MCP was effective to enhance the storage quality and lengthen the life span of apples. PRACTICAL APPLICATIONS: Jonah king apple has the characteristics of crisp texture, long shelf life, high sugar content, and solidity-acid ratio, which is suitable for the taste of east and southeast Asian. However, as for a kind of respiration climacteric fruit, the commercial quality of Jonah king apple dramatically drops during the later stage of storage due to its softening, superficial scald, and perishability. One of the primary problems in apple preservation is the reduction of microbial growth, which directly affects the internal quality of apple fruit. The aim of present work is to estimate the effect of ultrasonic plus 1-MCP treatment on storage quality and life span of apple fruit, as well as to provide theoretical basis to enhance the storage quality and lengthen the life span of apples.

Excessive phosphorus caused inhibition and cell damage during heterotrophic growth of Chlorella regularis.

A high phosphorus concentration is widely accepted as favorable for enhancing both microalgae growth and lipid accumulation; however, excessively high P could be counter-productive. In this study, we investigated the effects of increasing P levels (5.4, 25, 45, 150, and 250 mg-P L-1) on the heterotrophic cultivation of Chlorella regularis. Microalgae growth was inhibited and cells were severely damaged in response to highly excessive P levels (≥150 mg-P L-1). In particular, 250 mg-P L-1 resulted in a ∼40% decrease in cell density and a ∼70% loss of cell viability. Microalgae damage induced by excessive phosphorus included enlarged cell size, deformation of cell walls, and disorganization of organelles. These negative effects were associated with the over-accumulation of polyphosphates within cells, which may further cause binding of P to intracellular components. Although P is an essential nutrient, excessive P lowers cell growth and viability.

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success.

BACKGROUND: Renal denervation has no validated marker of procedural success. We hypothesized that successful renal denervation would reduce renal sympathetic nerve signaling demonstrated by attenuation of α-1-adrenoceptor-mediated autotransfusion during the Valsalva maneuver. METHODS AND RESULTS: In this substudy of the Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension, we enrolled 23 subjects with resistant hypertension. They were randomized either to bilateral renal denervation using therapeutic levels of ultrasound energy (n=12) or sham application of diagnostic ultrasound (n=11). Within-group changes in autonomic parameters, office and ambulatory blood pressure were compared between baseline and 6 months in a double-blind manner. There was significant office blood pressure reduction in both treatment (16.1±27.3 mm Hg, P<0.05) and sham groups (27.9±15.0 mm Hg, P<0.01) because of which the study was discontinued prematurely. However, during the late phase II (Iii) of Valsalva maneuver, renal denervation resulted in substantial and significant reduction in mean arterial pressure (21.8±25.2 mm Hg, P<0.05) with no significant changes in the sham group. Moreover, there were significant reductions in heart rate in the actively treated group at rest (6.0±11.5 beats per minute, P<0.05) and during postural changes (supine 7.2±8.4 beats per minute, P<0.05, sit up 12.7±16.7 beats per minute, P<0.05), which were not observed in the sham group. CONCLUSIONS: Blood pressure reduction per se is not necessarily a marker of successful renal nerve ablation. Reduction in splanchnic autotransfusion following renal denervation has not been previously demonstrated and denotes attenuation of (renal) sympathetic efferent activity and could serve as a marker of procedural success. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02029885.

Modulation of Neurally Mediated Vasodepression and Bradycardia by Electroacupuncture through Opioids in Nucleus Tractus Solitarius.

Stimulation of vagal afferent endings with intravenous phenylbiguanide (PBG) causes both bradycardia and vasodepression, simulating neurally mediated syncope. Activation of µ-opioid receptors in the nucleus tractus solitarius (NTS) increases blood pressure. Electroacupuncture (EA) stimulation of somatosensory nerves underneath acupoints P5-6, ST36-37, LI6-7 or G37-39 selectively but differentially modulates sympathoexcitatory responses. We therefore hypothesized that EA-stimulation at P5-6 or ST36-37, but not LI6-7 or G37-39 acupoints, inhibits the bradycardia and vasodepression through a µ-opioid receptor mechanism in the NTS. We observed that stimulation at acupoints P5-6 and ST36-37 overlying the deep somatosensory nerves and LI6-7 and G37-39 overlying cutaneous nerves differentially evoked NTS neural activity in anesthetized and ventilated animals. Thirty-min of EA-stimulation at P5-6 or ST36-37 reduced the depressor and bradycardia responses to PBG while EA at LI6-7 or G37-39 did not. Congruent with the hemodynamic responses, EA at P5-6 and ST36-37, but not at LI6-7 and G37-39, reduced vagally evoked activity of cardiovascular NTS cells. Finally, opioid receptor blockade in the NTS with naloxone or a specific µ-receptor antagonist reversed P5-6 EA-inhibition of the depressor, bradycardia and vagally evoked NTS activity. These data suggest that point specific EA stimulation inhibits PBG-induced vasodepression and bradycardia responses through a µ-opioid mechanism in the NTS.

Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses.

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the DRG at these spinal levels with intrathecal injection of TRPV1-siRNA, expression of phosphorylated ERK in the DRG neuron was reduced in MA-treated, but not EA-treated animals. These data suggest that TRPV1 in Group III and IV bimodal sensory afferent nerves contributes to acupuncture inhibition of reflex increases in blood pressure and specifically plays an important role during MA but not EA.