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Arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells:comparison of vasorelaxant effects of verapamil and phentolamine

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Acta Pharmaceutica Sinica B 2017年第3期7卷 319-325页

作者： Jing Jin Xin Shen Yu Tai Shanliang Li Mingyu Liu Changlin Zhen Xiuchen Xuan Xiyue Zhang Nan Hu Xinzi Zhang Deli Dong Department of Pharmacology(the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150086China Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150086China

Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine(PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K^+(KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PEbut not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE-and KPSSinduced aorta constriction. Transmission electron microscopy(TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells,and verapamil prevented both PE-and KPSS-induced excessive mitochondrial fission in aortic smoothmuscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells(A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.

关键词： Artery Mitochondrial fission phentolamine Vasorelaxation Verapamil

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Effect of phentolamine on myocardial extracellular matrix of cardiac remodeling in rats

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Asian Pacific Journal of Tropical Medicine 2014年第8期7卷 645-649页

作者： Yi-Gang Yin Ru-Zhu Wang Zhong-Bao Ruan Li Zhu Cardiovascular Institute People's Hospital of Taizhou

Objective:To study the effects of phentolamine on myocardial extracellular matrix of cardiac remodeling induced by norepinephrine in rats.Methods:24 SD rats were divided into 3 groups randomly:control groups,norepinephrine groups(model groups),norepinephrine +phentolamine groups(treatment groups).Echocardiography was used to detect changes in cardiac structure and function,the level of collagen volume fraction(CVF) and hydroxy-proline as well as collagen content were determined in myocardial tissue,matrix metalloproteinases-2 and collagen Ⅰin myocardial tissue were localized by immunohistochemitry.Results:Compared with control groups,left ventricular hypertrophy in the model group rats,the livdioxyproline content and CVF was significantly higher(Pphentolamine significantly improved cardiac hypertrophy in treatment group rats,reduced hydroxy-proline,CVF,matrix metalloproteinase 2and collagen Ⅰ protein expression(Pphentolamine can effectively reduce the incidence of myocardial hypertrophy and myocardial extracellular matrix remodeling in SD rats,and it can ease myocardial extracellular matrix of cardiac remodeling.It may he associated with reduced expression of matrix metalloproteinase 2 and collagen Ⅰ in myocardial tissue remodeling.

关键词： phentolamine 矩阵 metalloproteinases 骨胶原我细胞外的矩阵

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The Antagonized Effect of phentolamine on Endogenous Opiate-Like Substances

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Journal of Medical Colleges of PLA 1986年第1期 83-86页

作者：范谨之王正洪 Department of Physiology Fourth Military Medical College Xi’an

To study the relationship between OLS and adrenergic neurotransmis-sion is the purpose of this work.The inhibitory effect of phentolamine(5×10-8M)on OLS was observed.The results showed that on the basiccontraction of myenteric plexus longitudinal muscle（MPLM）,phentolaminehad no direct effects;phentolamine could not antagonize the light dose(2×10-7M)of NE-inhibitory on MPLM basic contraction;light dose phento-1amine could antagonize the inhibitory effect of OLS induced by high fre-quence（10Hz）stimulation to the MPLM basic contraction;phentolaminecould potentiate the effect of naloxone in antagonizing the OLS. For re-searching the interaction of adrenergic and enkephalinergic neurotransmis-sion,the present results may be helpful,and also provide a new idea aboutresearching the reeeptokinetics of two types of receptor.

关键词： opiate-like substance(OLS) naloxonenorepinephrin(NE) phentolamine myenteric plexus longitudinal muscle

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Effects　of　phentolamine　on　Hemorrheology　and　Hemodynamics　in　Dogs　with　Acute　Liver　Damage

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1996年第3期16卷 164-167页

作者：但自力张文英李绍白

The effects of phentolamine on hemorrheology and hemodynamics were studied in dogs with acute liver damage induced by acetaminophen. After 1 h of phentolamine application , the viscosity of plasma and whole blood was significantly diminished. The hematocrit readings followed the same pattern as the alterations in viscosity. The portal venous resistance and the value of K were remarkably decreased and the portal venous blood flow was obviously increased. It can be assumed , therefore , that the decrease in viscosity induced by phentolamine results from internal hemodilution and phentolamine may improve hepatic blood circulation through the decrease of portal venous resistance caused by the reduction of blood viscosity and the dilation of portal vascular beds.

关键词： phentolamine blood viscosity hemdynamics acute liver damage liver circulation hemodilution

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Curative effect of silybin combined with pituitrin-phentolamine for pulmonary tuberculosis complicated by acute hemoptysis

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Journal of Hainan Medical University 2017年第24期23卷 37-40页

作者： Shu-Hua Li Li-Jun Zou Department of Infectious Diseases Hanchuan City People's Hospital in Hubei ProvinceHanchuanHubei Province431600 Department of Emergency Hanchuan People's Hospital in Hubei ProvinceHanchuanHubei Province431600

Objective: To study the curative effect of silybin combined with pituitrin-phentolamine for pulmonary tuberculosis complicated by acute hemoptysis. Methods: A total of 78 patients with pulmonary tuberculosis complicated by acute hemoptysis who were treated in this hospital between December 2013 and April 2017 were divided into control group (n=39) and silybin group (n=39) by random number table. Control group received pituitrin-phentolamine hemostasis therapy, silybin group received pituitrin-phentolamine combined with silybin therapy, both were treated for 1 week. The differences in peripheral blood liver function and coagulation index levels as well as serum oxidative stress index contents were compared between the two groups of patients before treatment and after 1 week of treatment. Results:Before treatment, the differences in peripheral blood liver function and coagulation index levels as well as serum oxidative stress index contents were not statistically significant between the two groups. After 1 week of treatment, peripheral blood liver function indexes ALT, AST, ALP and STB contents of silybin group were lower than those of control group;peripheral blood coagulation indexes PT, APTT and TT levels were lower than those of control group whereas Fib level was higher than that of control group;serum oxidative stress indexes AOPPs and LHP contents were lower than those of control group whereas GSH-Px and T-AOC contents were higher than those of control group. Conclusion: pituitrin-phentolamine combined with silybin therapy can effectively protect the liver function, optimize the coagulation function and reduce the oxidative stress response in patients with pulmonary tuberculosis complicated by acute hemoptysis.

关键词： Pulmonary tuberculosis Cute hemoptysis Silybin Pituitrin phentolamine

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Vasorelaxant effect of osthole on isolated thoracic aortic rings in rats

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Journal of Traditional Chinese Medicine 2019年第4期39卷 492-501页

作者： Huang Ying Kong Liting Wang Yanping Sun Mingjie Cui Haifeng Zhai Huaqiang LüCheng Fan Danping Experimental Research Center China Academy of Chinese Medical SciencesBeijing 100700China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China

OBJECTIVE: To investigate the effect of osthole on isolated thoracic aortic rings, and to determine the potential mechanism of action.METHODS: Thoracic aortas were isolated from Wistar rats, and were suspended in tissue organ chambers for vascular tension measurement. The effect of cumulative osthole(10-9, 10-8, 10-7, 10-6, and 10-5 mol/L) on endothelium-intact and endothelium-denuded thoracic aortic rings pre-contracted with phenylephrine(PE, 10-6 mol/L) or KCl(6 × 10-2 mol/L) was recorded. Histomorphological changes of thoracic aorta were analyzed by hematoxylin-eosin. The effects of different osthole concentrations on endothelium-intact aortic rings, which were pre-inhibited with the non-selective nitric oxide synthase inhibitor L-Arg(NO2)-OMe·HCl(3 × 10-4 mol/L), endothelium-derived nitric oxide synthase inhibitor Nω-nitro-L-arginine(3 × 10-4 mol/L), guanylate cyclase inhibitor 1 H-[1,2,4] oxadiazolo [4,3-α]quinoxaline-1-one(10-5 mol/L), cyclooxygenase inhibitor indometacin(10-5 mol/L), and the Ca2+-activated potassium channel inhibitor tetraethylammonium nitrate(10-5 mol/L), and then contracted with PE, were examined. Aortic rings incubated with osthole(10-5 mol/L), phentolamine(10-5 mol/L), or verapamil(10-5 mol/L) in Ca2+-free Krebs-Henseleit solution(KHS) were stimulated with PE or KCl.RESULTS: There was a dose-dependent increase in vasorelaxation of isolated thoracic aortic rings(both with and without endothelium) with increasing osthole concentration. Hematoxylin-eosin staining showed that osthole significantly improved thoracic aorta ring morphology. Compared with the control group, there were also significant differences after incubation with L-Arg(NO2)-OMe ω-nitro-L-arginine, and 1 H-[1,2,4] oxadiazo·lo HCl,N [4,3-α] quinoxaline-1-one(P < 0.05 for all). The relaxation rate of the rings in the osthole group incubated with indometacin and tetraethylammonium nitrate were similar to controls. In Ca2+-free KHS, the PE-induced contraction was similar between the osthole(4.37% ± 0.41%) and control(4.21% ± 1

关键词： Aorta,thoracic Osthole phentolamine Verapamil Vasorelaxation Calcium Nitric oxide

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Effect of catecholamines on IL-2 production and NK cytotoxicity of rats in vitro

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Acta Pharmacologica Sinica 2004年第10期 114-120页

作者： Yu-ping PENG, Yi-hua QIU, Jian-lan JIANG, Jian-jun WANGDepartment of Biological Science and Technology and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093 Department of Physiology and Jiangsu Key Laboratory of Neurore generation,Nantong Medical College, Nantong 226001, China

AIM: To explore effects of exogenous and endogenous catecholamines on function of lymphocytes and primary mechanisms mediating the effects. METHODS: Splenocytes of rats were exposed to norepinephrine (NE), a- or p-adrenoceptor antagonists plus NE, or α-methyl-p-tyrosine (α-MT), and then concanavalin A (Con A)-induced interleukin-2 (IL-2) production and natural killer (NK) cell cytotoxicity were determined by MTT assay and LDH assay, respectively. RESULTS: Optical density (OD) values of NE-treated groups, which reflected IL-2 production, were 0.63, 0.61, and 0.60, respectively for 1×10-10, 1×10-9, and 1×10-8 mol/L NE. They were all significantly reduced in comparison with control value of 0.68 (Pphentolamine (an α-adrenoceptor antagonist) or propanolol (a β-adrenoceptor antagonist). OD values of α-MT, an inhibitor of tyrosine hydroxylase, at doses of 1×10-10,1×10-9, and 1×10-8 mol/L respectively were 0.71, 0.71, and 0.69, which were all notably hig

关键词： catecholamines norepinephrine phentolamine propranolol α-methyl-p-tyrosine interleukin-2 natural killer cell

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Effect of norepinephrine or phentolamine microinjected into caudate nucleus on the pain threshold of rat tail-flick

Effect of norepinephrine or phentolamine microinjected into ...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Guang-Wen ZHANG~1,Duo ZHANG~2,He-Ren GAO~2,Yu LIANG~3,Ying HANG~2,Run-Sheng JIAO~2,Hui ZHANG~2,Man-Ying XU~(2,*) 1 Third Affiliated Hospital 2 Laboratory of Neural Electrophysiology,Department of Physiology,Harbin Medical University,Harbin 150081, China 3 Mudanjiang Medical College,Mudanjiang 157000,China

＜正＞Objective To investigate the influences of caudate nucleus injection of different doses alpha-adrenoceptor agonist norepinephrine（NE） or antagonist phentolamine on the pain threshold of rat tail-flick.Methods The tail-flick latency（TFL） of rat was recorded using the thermal pain stimulator.To measure the effects of the caudate nucleus injection of NE（2μg/2μl or 8μg/2μl）,phentolamine（1μg/2μl or 4μg/2μl） or normal saline（2μl） on TFL.Results The caudate nucleus injection of the higher dose of 8μg NE shortened the TFL,the higher dose of 4μg phentolamine lengthened the TFL（P＜0.01）.However,injection of the lower dose of 2μg NE into the caudate nucleus lengthened the TFL,the lower dose of 1μg phentolamine shortened the TFL（P＜0.01）.Conclusion Injection of alpha-adrenoceptors agonist 2μg NE into the caudate nucleus produced the antinociceptive effects on the responses to noxious thermal stimulation in tail-flick tests. However,injection of 8μg NE into the caudate nucleus caused hyperalgesic actions.In contrast,injection of alpha-adrenoceptors antagonist phentolamine 1μg into the caudate nucleus produced hyperalgesic actions on the responses to noxious thermal stimulation in tail-flick tests,4μg caused analgesic effects.These results indicate that the caudate nucleus of rat injection of different doses of NE or phentolamine have opposing effects,i.e.,exhibiting the analgesic effect or the hyperalgesic effect.It is revealed that the effects of different doses NE in the caudate nucleus of the rat on the pain threshold of tail-flick are involved in the different subtypes of alpha-adrenoceptors.

关键词： Caudate nucleus norepinephrine phentolamine tail-flick latency

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The effects of scorpion(Buthus martensi Karsch)venom on rat left ventricular function

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Journal of Medical Colleges of PLA(China) 1992年第3期7卷 265-268页

作者：龚剑平龚彦德刘菊芳张永胜 Department of Pharmacology First Military Medical UniversityGuangzhou 510515

In order to investigate the cardiovascular effects of the scorpion(Buthus martensiKarsch)venom(BmKv),the left ventricle of the rats was catheterized via the right carotidartery.The LVP,LVEDP,+dp/dt max,Vmax,HR and BP were observed.The results showedthat intravenous injection of the BmKv(60μg/kg),in comparison with the control,elicited obvi-ous hypertension and increase of cardiac contractility,both of which lasted for 1h,while theheart rate had no significant change rand that pretreating the rats with alpha-adrenergic blocker,phentolamine,antagonized the hypertensive effects,but did not antagonize the increase of cardiaccontractility.Pretreatment with beta-adrenergic blocker,propranolol,has no influence on the ef-fects of the venom.It is suggested that the hypertensive effects are due to the activation of al-pha-adrenergic receptor,whereas the increase of cardiac contractility may not be resulted fromthe activation of beta-adrenergic receptor.The BmKv treated with dithiothreitol before injectionhad no cardiovascular effects,indicating that the intact disulfide bridges play a decisive role inthe cardiovascular effects of the BmKv.

关键词： Buthus martensi Karsch scorpion venoms phentolamine propranolol dithiothreitol myocardial contraction blood pressure animal rats

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Imidazolines促胰岛素分泌作用机制的研究

Imidazolines促胰岛素分泌作用机制的研究

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作者：梁日欣 Institute of Chinese Materia Medica China Academy of Traditional Chinese Medicine

目的:观察imidazolines:phentolamine,efaroxan和idazoxan对ATP调节的钾离子通道的影响,从而探讨其促胰岛素分泌的作用机制。方法:用"内面向外"的膜片钳制技术,在培养的无性系的RINm5F胰岛素分泌细胞进行实验。结果:phentolamine 50μmo... 详细信息

目的:观察imidazolines:phentolamine,efaroxan和idazoxan对ATP调节的钾离子通道的影响,从而探讨其促胰岛素分泌的作用机制。方法:用"内面向外"的膜片钳制技术,在培养的无性系的RINm5F胰岛素分泌细胞进行实验。结果:phentolamine 50μmol·L明显抑制ATP调节的钾离子通道,显著降低通道开放的概率。Efaroxan 50μmol·L明显降低通道开放的概率,抑制钾离子通道的开放,但作用维持时间短。idazoxan 50μmol·L对通道开放概率的影响不明显。结论:phentolamine,efaroxan和idazoxan促胰岛素分泌的作用与阻断ATP调节的钾离子通道有关。

关键词： RINm5F 膜片钳制技术 phentolamine efaroxan idazoxan

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