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Axonotmesis-evoked plantar vasodilatation as a novel assessment of C-fiber afferent function after sciatic nerve injury in rats

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Neural Regeneration Research 2019年第12期14卷 2164-2172页

作者： Xue-Song Wang Xue Chen Tian-Wen Gu Ya-Xian Wang Da-Guo Mi Wen Hu Department of Orthopedics The Affiliated Hospital of Jiangnan University (The Third People’s Hospital of Wuxi City) Wuxi Jiangsu Province China Wuxi School of Medicine Jiangnan University Wuxi Jiangsu Province China Key Laboratory for Neuroregeneration of Ministry of Education and Co-innovation Center for Neuroregeneration of Jiangsu Province Nantong University Nantong Jiangsu Province China Department of Orthopedics Nantong Hospital of Traditional Chinese Medicine Nantong Jiangsu Province China

Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.

关键词： nerve regeneration axonotmesis-evoked vasodilatation laser Doppler perfusion imaging nerve function autonomic nerve C-fiber afferent function peripheral nerve injury unmyelinated afferent fiber regeneration neural regeneration

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Paeonol Induces vasodilatation in Rat Mesenteric Artery via Inhibiting Extracellular Ca^(2+) Influx and Intracellular Ca^(2+) Release

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Chinese Journal of Integrative Medicine 2013年第7期19卷 510-516页

作者：张金艳曹永孝翁维良李贻奎赵乐 Experiment and Research Center Xiyuan HospitalChina Academy of Chinese Medical Sciences Department of Pharmacology College of Medicinexi'an Jiaotong University

To investigate the vasodilative effect of paeonol in rat mesenteric artery and the mechanisms responsible for it. Methods： Rats were anaesthetized and sacrificed. The superior mesenteric artery was removed, dissected free of adherent tissue and cut into 2.0 mm long cylindrical segments. Isometric tension of artery rings was recorded by a myograph system in vitro. Concentration-relaxation curves of paeonol （17.8 μmol/L to 3.16 mmol/L） were recorded on artery rings precontracted by potassium chloride （KCI） and concentration-contraction curves of KCI, 5-hydroxytryptamine （5-HT）, noradrenaline （NA） or calcium chloride （CaCI2） were recorded in the presence of paeonol （10^-4.5, 10^-3.8, 10^-3.5 tool/L） respectively. And also, concentration- relaxation curves of paeonol were recorded in the presence of different potassium channel inhibitors and propranolol on rings precontracted with KCI respectively. To investigate the role of intracellular Ca2. release from Ca2. store, the contraction induced by NA （100μmol/L） and CaCI2 （2 mmol/L） in Ca^2＋ free medium was observed in the presence of paeonol respectively. Results： Paeonol relaxed artery rings precontracted by KCI in a concentration-dependent manner and the vasodilatation effect was not affected by endothelium denudation. Paeonol significant decreased the maximum contractions （Emax） induced by KCI, CaCl2, NA and 5-HT, as well as Emax induced by NA and CaCI2 in Ca^2＋-free medium, suggesting that paeonol dilated the artery via inhibiting the extracellular Ca2. influx mediated by voltage-dependent calcium channel, and receptor-mediated Ca^2＋-influx and release. Moreover, none of glibenclamide, tetraethylammonium, barium chlorded and propranolol affected the paeonol-induced vasodilatation, indicating that the vasodilatation was not contributed to ATP sensitive potassium channel, calcium-activated potassium channel, inwardly rectifying potassium channel, and β-adrenoceptor. Conclusion： Paeonol induces non-endothelium dependent-vasodilatation in rat mesenteric artery via inhi

关键词： paeonol vasodilatation contraction rat mesenteric artery calcium

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Imperatorin Is Responsible for the vasodilatation Activity of Angelica Dahurica var. Formosana Regulated by Nitric Oxide in an Endothelium-Dependent Manner

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Chinese Journal of Integrative Medicine 2009年第6期15卷 442-447页

作者：聂红孟兰贞周玖瑶樊晓峰罗勇张广文 College of Pharmacy Jinan University Guangzhou University of Chinese Medicine Research Center for Analytical Sciences of Northeastern University College of Science and Engineering Jinan University

Objective:To demonstrate the vasodilatation activity of the coumarin-containing Angelica dahurica var.formosana and to further analyze active components in the herb extracts.Methods:(1) The vasodilatation effects induced by different extracts(cyclohexane,ethyl acetate,acetone,methanol,95%ethanol and water) of Angelica dahurica var.formosana on mouse thoracic aorta pre-contracted with phenylephrine were investigated. (2) The amount of imperatorin and isoimperatorin in each extract was measured by high-performance liquid chromatography.(3) The vasodilatation effects of imperatorin and isoimperatorin on mouse thoracic aorta were compared using the same in vitro method.(4) The vasodilatation mechanism of imperatorin in the mouse thoracic aorta pre-contracted with phenylephrine was studied using the methods of denuded endothelium, NG-nitro-L-arginine methylester(L-NAME,a nitric oxide synthase inhibitor),and propranolol.Results:(1) The cyclohexane and ethyl acetate extracts of Angelica dahurica var.formosana decreased the maximal response of phenylephrine-induced mouse thoracic aorta contraction dose-dependently,with 50%inhibiting concentration (IC50) values of 35.3±12.4 mg/L and 40.5±12.0 mg/L,respectively.The vasodilatation effect of imperatorin and isoimperatorin was dose-dependent.(2) The cyclohexane extract,showing the strongest vasodilatation effect,possessed the highest contents of imperatorin(4.09%) and isoimperatorin(0.27%,w/w).There was a correlation between the vasodilatation activity and the contents of imperatorin and isoimperatorin in the extracts. (3) The vasodilatation effect of imperatorin was about 4-fold stronger than that of isoimperatorin.(4) The vasodilatation effect of imperatorin was significantly attenuated to 24.88%±4.06%in the denuded endothelium group compared with the intact endothelium group.And 1 mmol/L L-NAME reduced the imperatorin-induced vasorelaxation by 32.18%±11.29%.Conclusions:The principal effective component of Angelica dahurica var. Formosana was found to be imperatorin.Imperat

关键词： Angelica dahurica var.formosana thoracic aorta vasodilatation imperatorin isoimperatorin high-performance liquid chromatography

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Combined antihypertensive effect of GSY and metoprolol,based on endothelium-dependent vasodilatation function

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中国药理学与毒理学杂志 2015年第S1期29卷 38-39页

作者： BoLI JieSU Shan-shanLEI Zheng-biaoYANG Ze-wuJIN Hui-mingHU En-weiZHU Gui-yuanLYU Su-hongCHEN Zhejiang Chinese Medical University Hangzhou 310053 China Wenzhou Medical University Wenzhou 325035 China

OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).

关键词： hypertension endothelium-dependent vasodilatation

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The relation of flow-mediated vasodilatation and diastolic function in uncomplicated Type 2 diabetic patients

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Journal of Diabetes Mellitus 2013年第2期3卷 39-44页

作者： J. Charvat J. Chlumsky P. Svab M. Peckova Department of Medicine 2nd Medical Faculty Charles University and Faculty Hospital Motol Prague Czech Republic

Objectives: To evaluate the association of diastolic function of the left ventricle with flowme-diated dilatation (FMD) in uncomplicated Type 2 diabetes mellitus patients. Methods: Eighty-two uncomplicated Type 2 diabetic patients were examined by pulse and tissue Doppler echocardiography and FMD of brachial artery. The patients were divided into 2 groups according to the size of the left ventricular relaxation parameter—E’. Results: The average age of the patients was 61 ± 6 years. FMD was 5.0 ± 1.8% in 41 patients with E’ from 3 to 7.4 cm/s (mean 6 cm/s) comparing to 5.1 ± 1.9% (p = 0.96) in 41 patients with E’ from 7.5 to 10.9 cm/s (mean 8.9 cm/s). E/E’ was 11.2 ± 2.3 in the group with lower E’ and 9.1 ± 1.6 in the group with higher E’ (p 0.001). Linear negative correlation was found between E/E’ and FMD for the patients with E’ from 3 to 7.4 cm/s (R2 = 0.131;p = 0.025) but not for the group of patients with the higher E’. The significant association between FMD and E/E’ was confirmed by multivariate analysis ((Rc)2 = 0.233;p 0.05). Conclusion: FMD has no impact on the left ventricular relaxation. However FMD is negatively associated with E/E’ in Type 2 diabetic patients who have low E’ as a sign of an impaired early relaxation.

关键词： Flow-Mediated vasodilatation Tissue and Pulse Doppler Echocardiography Type 2 Diabetes Mellitus Diastolic Function Left Ventricular Relaxation

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The effect of aerobic training on endothelium-dependent vasodilatation in patients with coronary artery disease who were revascularized and young men

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Health 2013年第10期5卷 1706-1711页

作者： Seyed Masoud Seyedian Farzaneh Ahmadi Babak Hamidian Ebrahim Hajizadeh Afshin Rezazadeh Ahmad Reza Asare Mohammad Hasan Adel Mohammad Nourizadeh Atherosclerosis Research Center Joundishapour University Ahvaz Iran Cardiovascular Disease Research Center Joundishapour University Ahvaz Iran Cardiovascular Disease Research Center Jundishapur University Ahvaz Iran Department of Cardiology Medical Jundishapur University of Ahvaz Atherosclerosis Research Center Jondishapour University of Medical Sciences Ahvaz Iran

Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.

关键词： Endothelium-Dependent vasodilatation Coronary Artery Disease Aerobic Training High-Resolution Ultrasound Flow-Mediated Dilation

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Chilean crude extract of <i>Ruta graveolens</i>generates vasodilatation in rat aorta at subtoxic cellular concentrations

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Advances in Bioscience and Biotechnology 2013年第1期4卷 29-36页

作者： Ignacio Jofré Fernández Patricia Navarrete Gómez Jorge Parodi Fernando Romero Mejía Raúl Salvatici Salazar Center of Neurosciences and Peptides Biology Faculty of Medicine Universidad de La Frontera Temuco Chile Laboratorio de Fisiología de la Reproducción Núcleo de Producción Alimentaria Escuela de Medicina Veterinaria Facultad de Recursos Naturales Universidad Católica de Temuco Temuco Chile Laboratory of Molecular and Cellular Neurobiology Department of Molecular and Cellular Neurobiology Neurobiology Institute Campus Juriquilla-Querétaro Universidad Nacional Autónoma de México Mexico City Mexico

In Chile elevated percentage of population have cardiovascular diseases, 70% of this populations is a hypertensive peoples. The Ruta graveolens (Ruta) is a medicinal plant used in different parts of the world with different therapeutics properties like dermatologic as far as anti-helmintic properties. We analyzed the vascular action measuring the tension to identify vasodilator effect of Ruta extract in norm-tense rat’s aorta incubated and measured in isolated organ bath, and evaluating the toxicity effect in CRL-1730 cell line, through enzymatic assay (MTT), confocal microscopy (propidium iodide stain) and flow cytometry (TUNEL assay), including extracellular reactive oxygen species (ROS) production through luminescence assay. The results show with DE50 29 ± 0.1 μg/mL evidenced vasodilatation, partially endothelium-depend. The cytotoxicity showed with DE50 304.6 ± 2 μg/mL in enzymatic assay (MTT) while evidenced membrane permeability in high concentrations (1500 μg/mL), DNA fragmentation in absence of oxidative stress in only observed when high concentrations of Ruta are used over the cell culture. The vasodilatation activity is executed in subtoxic concentration and partially endothelium-depend without permeability effect in the membrane and deterioration of the cells viability suggesting a complex effect of Ruta preparation in the regulation of vascular tone.

关键词： vasodilatation Ruta graveolens Toxicity Endothelium

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Plants Used as Antihypertensive

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Natural Products and Bioprospecting 2021年第2期11卷 155-184页

作者： Tarawanti Verma Manish Sinha Nitin Bansal Shyam Raj Yadav Kamal Shah Nagendra Singh Chauhan I.K.Gujral Punjab Technical University(IKGPTU) JalandharPunjabIndia Laureate Institute of Pharmacy KathogJwalamukhiKangraHimachal PradeshIndia Department of Pharmacology ASBASJSM College of PharmacyBELARoparPunjabIndia Department of Chemistry S.P.Jain College(Veer Kunwar Singh UniversityAra)SasaramBiharIndia Institute of Pharmaceutical Research GLA UniversityNH#2MathuraUttar Pradesh 281406India Drugs Testing Laboratory Avam Anusandhan Kendra 1st Floor Govt.Ayurvedic Hospital BuildingGovt.Ayurvedic College Campus G.E.RoadRaipurChhattisgarh 492010India

Hypertension is a critical health problem and worse other cardiovascular diseases.It is mainly of two types:Primary or essential hypertension and Secondary hypertension.Hypertension is the primary possibility feature for coronary heart disease,stroke and renal vascular disease.Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects.Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms,from the bottom of cell culture and ex-vivo tissue data.According to WHO,natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body.Plants are the regular industrial units for the invention of chemical constituents,they used as immunity booster to enhance the natural capacity of the body to fight against different health prob-lems as well as herbal medicines and food products also.Eighty percent population of the world(around 5.6 billion people)consume medicines from natural plants for major health concerns.This review provides a bird’s eye analysis primarily on the traditional utilization,phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e.Hibiscus sabdariffa,Allium sativum,Andrographis paniculata,Apium graveolens,Bidenspilosa,Camel-lia sinensis,Coptis chinensis,Coriandrum sativum,Crataegus spp.,Crocus sativus,Cymbopogon citrates,Nigella sativa,Panax ginseng,Salviaemiltiorrhizae,Zingiber officinale,Tribulus terrestris,Rauwolfiaserpentina,Terminalia arjuna etc.

关键词： Hypertension Antihypertensive herbs Blood pressure vasodilatation Herbal medicines Blood pressure regulation

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Pharmacological characteristics of Kampo medicine as a mixture of constituents and ingredients

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Journal of Integrative Medicine 2013年第1期11卷 11-16页

作者： Hiroyasu Satoh Health Life Science Shitennoji UniversityHabikino Osaka 583-8501 Japan

Herbal medicine in Japan is termed as Kampo medicine, which is derived from traditional Chinese medicine. Shakuyakukanzoto （Shao-Yao-Gan-Cao-Tang） as a kind of Kampo formulations is composed of just two components; Paeoniae Radix and Glycyrrhizae Radix, which produced marked relaxation of intestinal tract. Mokuboito （Mu-Fang-Ji-Tang） inhibited cardiac ionic channel currents, and as a mixture also produced great vasodilatation. Sinomenine （a main ingredient of Mokuboito） as a single compound also caused the vasodilatation, but decreased it along with ageing. Gypsum containing in Mokuboito and Chotosan （Diao-Teng-San） caused more marked effects, as compared with those without Gypsum. On the other hand, Rokumigan （Liu-Wei-Wan）, Hachimijiogan （Ba-Wei-Di-Huang-Wan） and Goshajinkigan （Niu- Che-Shen-Qi-Wan） increase in order the number of contained ingredients. The formulations with more herbs （ingredients） produced much more effective actions on rat aorta, presumably due to compensation of the decline of pharmacological sensitivity with ageing. Thus, there are some important differences between single chemical drugs and mixture drugs with many ingredients. The effects of Kampo medicine （mixture） are never just a sum of each effect induced by a lot of in qredients. For elder persons, furthermore, Kampo medicine exerts more effective actions.

关键词： Kampo medicine multiple compounds medicine, herbal anti-ageing drugs vasodilatation rats

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Therapeutic potential of targeting the renin angiotensin system in portal hypertension

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World Journal of Gastrointestinal Pathophysiology 2013年第1期4卷 1-11页

作者： Chandana B Herath Josephine A Grace Peter W Angus Department of Medicine University of MelbourneAustin HealthHeidelberg Victoria 3084Australia Department of Gastroenterology Austin HealthHeidelbergVictoria 3084Australia

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered "alternate axis" of the RAS.

关键词： Angiotensin-(1-7) Portal hypertension Intrahepatic resistance Mesenteric vasodilatation Variceal bleeding Non-selective b-blockers Renin angiotensin system Mas receptor Angiotensin receptor Cirrhosis

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