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Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and calcium channel blocker in Patients with Hypertension and Chronic Kidney Disease

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Chinese Medical Journal 2016年第5期129卷 562-569页

作者： Rong-Shuang Huang Yi-Ming Cheng Xiao-Xi Zeng Sehee Kim Ping Fu Department of Internal Medicine Renal Division West China Hospital of Sichuan University Chengdu Sichuan 610041 China West China Biostatistics and Cost-Benefit Analysis Center West China Hospital of Sichuan University Chengdu Sichuan 610041 China Department of Biostatistics University of Michigan Ann Arbor Michigan 48109 USA

Background：Renin-angiotensin system inhibitor and calcium channel blocker （CCB） are widely used in controlling blood pressure （BP） in patients with chronic kidney disease （CKD）.We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） and CCB （i.e.,ACEI/ARB ＋ CCB） with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods：Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials （RCTs） of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease （ESRD）,cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate （GFR）,and adverse events were extracted.Results：Based on seven RCTs with 628 patients,ACEI/ARB ＋ CCB did not show additional benefit for the incidence of ESRD （risk ratio [RR] =0.84;95% confidence interval [CI]：0.52-1.33） and cardiovascular events （RR =0.58;95% CI：0.21-1.63） significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP （weighted mean difference [WMD] =-1.28 mmHg;95% CI：-3.18 to-0.62）,proteinuria （standard mean difference =-0.55;95% CI：-1.41 to-0.30）,GFR （WMD =-0.32 ml/min;95% CI：-1.53 to-0.89）,and occurrence of adverse events （RR =1.05;95% CI：0.72-1.53）.However,ACEI/ARB ＋ CCB showed a greater reduction in systolic BP （WMD =-4.46 mmHg;95% CI：-6.95 to-1.97）,compared with ACEI/ARB monotherapy.Conclusion：ACEI/ARB ＋ CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.

关键词： calcium channel blocker Chronic Kidney Disease Hypertension Renin-angiotensin System Inhibitor Renoprotection Therapy

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Inhibition of calcium channel blocker associated with lowering C-reactive protein level in rupture of abdominal aortic aneurysm

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South China Journal of Cardiology 2010年第4期11卷 228-233,256页

作者：王建国李世军杨庭树 Division of Geriatric of Cardiology Chinese PLA General Hospital

Background As to abdominal aortic aneurysm （AAA） disease, our major challenge faced in clinical practice is effective drug therapies to prevent rupture of AAA. At present, there wasn’t definite evidence that other drugs had a role in inhibiting AAA rupture except for beta blocker. In our study, we evaluated the role of calcium channel blocker （CCB） played in prevention of AAA rupture. Methods A total of 460 subjects with AAA, aged 29 to 89 years, at least twice admitted into our hospital from January 2000 to April 2010. All of them accepted ultrasound examination for scanning abdominal aortic aneurysm at each admission period. Results Our results revealed that AAA patients suffered from rupture took little CCB and beta-blockers. Treatment with CCB or beta blocker was negatively related to risk of rupture of abdominal aortic aneurysm, and drugs such as statins, angiotensin II receptor blocker （ARB） or angiotensin-converting enzyme inhibitor （ACEI） hadn’t positive or negative effect on AAA. C reactive protein level was lower in patients with taking CCB than those without CCB. Conclusions CCB therapy was negatively related to AAA rupture, and possibly was another kind of drug for.

关键词： abdominal aortic aneurysm rupture calcium channel blocker

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calcium channel blockers and Alzheimer's disease

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Neural Regeneration Research 2012年第2期7卷 137-140页

作者： Yi Tan Yulin Deng Hong Qing School of Life Science Beijing Institute of Technology Beijing 100081 China

Alzheimer＇s disease is characterized by two pathological hallmarks： amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer＇s disease. calcium channel blockers are effective therapeutics for treating Alzheimer＇s disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer＇s disease theraov.

关键词： Alzheimer＇s disease caic-ium channel calcium homeostasis Alzheimer＇s diseasepathogenesis β-amyloid calcium channel blocker

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Association between common cardiovascular drugs and depression

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Chinese Medical Journal 2021年第22期134卷 2656-2665页

作者： Shu-Hui Tao Xue-Qun Ren Li-Jun Zhang Mei-Yan Liu Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China Department of Medicine Henan UniversityKaifengHenan 475001China.

Objective:Cardiovascular diseases are associated with an increased risk of depression,but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk.The effects of drugs on individual usage are also often unknown.This review aimed to examine the correlation between depression and common cardiovascular drugs,develop more potent interventions for depression in cardiovascular patients,and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.Data sources:The data in this review were obtained from articles included in PubMed,EMBASE,and Web of Science.Study selection:Clinical trials,observational studies,review literature,and guidelines about depression and cardiovascular drugs were selected for the article.Results:We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review.Statins have been proven to have antidepressant effects.Some studies believe angiotensin-converting enzyme inhibitors(ACEIs)/angiotensin receptor blocker(ARB)can exert an antidepressant influence by acting on the renin-angiotensin system,but further clinical trials are needed to confirm this.Beta-blockers have previously been associated with depression,but the current study found no significant association between beta blockers and the risk of depression.Aspirin may have antidepressant effects by suppressing the immune response,but its role as an antidepressant remains controversial.calcium channel blockers(CCBs)can regulate nerve signal transduction by adjusting calcium channels,but whether this effect is beneficial or harmful to depression remains unclear.Finally,some cases have reported that nitrates and diuretics are associated with depression,but the current clinical evidence is insufficient.Conclusions:Statins have been proven to have antidepressant effect,and the antidepressant effects of ACEIs/ARB and aspirin are still controversial.CCBs are associated with depre

关键词： Depression Cardiovascular drugs Statins b-blockers calcium channel blocker

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Drug-induced gingival overgrowth in cardiovascular patients

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World Journal of Cardiology 2021年第4期13卷 68-75页

作者： Lucija Bajkovec Anna Mrzljak Robert Likic Ivan Alajbeg Institute of Emergency Medicine of Medimurje County Institute of Emergency Medicine of Međimurje CountyCakovec 40000Croatia Department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Unit for Clinical Pharmacology and TherapeuticsDepartment of Internal Medicine University Hospital Centre ZagrebZagreb 10000Croatia Department of Oral Medicine University of Zagreb School of Dental Medicine and University Hospital Centre ZagrebZagreb 10000Croatia

Drug-induced gingival overgrowth(DIGO)is a pathological growth of gingival tissue,primarily associated with calcium channel blockers and immunosuppressants.Consequently,it is mainly seen in cardiovascular and transplanted patients.Nifedipine remains the main calcium channel blocker related to the development of this unpleasant side-effect.As for immunosuppress-ants,cyclosporin is the leading causative agent,whereas other drugs from this druggroup,including tacrolimus,have better safety profiles.Accumulated collagen with inflammatory infiltrates is the histological hallmark of this condition.Several factors are involved in the pathogenesis and can increase the risk,such as male gender,younger age,pre-existing periodontal inflammation,and concomitant use of other DIGO-inducing medications.Patients with DIGO may experience severe discomfort,trouble with speech and mastication,pain,and teeth loss,aside from cosmetic implications.Furthermore,these patients also have an increased risk for cardiovascular diseases.The interdisciplinary approach and cooperation with dental care experts are necessary for patient management.Treatment includes discontinuing the drug and switching to one with a better profile,improving oral hygiene,and surgical removal of enlarged tissue.Recognizing the potential of commonly used medications to cause DIGO and its effect on patients'health is necessary for early detection and adequate management of this complication.

关键词： Drug-induced gingival overgrowth calcium channel blocker Nifedipine

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Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels

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Asian Pacific Journal of Tropical Biomedicine 2021年第5期11卷 214-221页

作者： Rabia Iqbal Irfan Hamid Khalid Hussain Janbaz Muhammad Furqan Akhtar Ammara Saleem Ali Sharif Sohaib Peerzada Bushra Akhtar Kashif Sohail Sajid Ali Faculty of Pharmacy The University of LahoreLahorePakistan Cadson College of Pharmacy University of the PunjabLahorePakistan Department of Pharmacology Bahauddin Zakariya UniversityMultanPakistan Riphah Institute of Pharmaceutical Sciences Riphah International UniversityLahore CampusLahorePakistan Department of Pharmacology Faculty of Pharmaceutical SciencesGovernment College University FaisalabadFaisalabadPakistan Department of Pharmacology Faculty of Pharmaceutical and Allied health SciencesLahore College for Women UniversityLahorePakistan Institute of Pharmacy Physiology and PharmacologyUniversity of AgricultureFaisalabadPakistan Akson College of Pharmacy Mirpur University of Science and TechnologyMirpurAJKPakistan

Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath.The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System.The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis,respectively.Results:The total phenolic and total flavonoids contents of the extract were(267.75±5.77)mg GAE/g and(73.86±6.01)mg QE/g,respectively.Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC_(50)value of 0.016 mg/m L,which was blocked by atropine(0.3μM).Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC_(50)value of 2.185 mg/mL.Furthermore,Argemone mexicana extract relaxed potassium(80 mM)-induced contractions(EC_(50):9.07 mg/mL),similar to a standard drug verapamil.The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract(1-5 mg/mL)and verapamil(0.1-1μM).In addition,the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks.Conclusions:Argemone mexicana shows cholinergic agonist and calcium channel blocker activities,as well as antiemetic effect.It may be used as a potential agent for treating gastrointestinal disorders.

关键词： Argemone mexicana Muscarinic agonist calcium channel blocker Constipation Emesis

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Antihypertensive efficacy of extract of Hedera helix in high salt-induced hypertensive Sprague-Dawley rats

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Asian Pacific Journal of Tropical Medicine 2018年第8期11卷 473-479页

作者： Umme Salma Taous Khan Abdul Jabbar Shah Cardiovascular Research Group Department of Pharmacy COMSATS University IslamabadAbbottabad campus

Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methanolic extract was prepared and the activity directed fractionation was carried out. Spectrophotometric analysis of total phenolic and flavonoid content was also done. HPLC analysis was performed for the detection of hederacoside C. In-vivo blood pressure study was carried out in normotensive and high salt-induced hypertensive SpragueDawley rats. Isolated aortic tissues from rat and rabbit were used for in-vitro studies. The effects were recorded and analyzed through PowerL ab data acquisition system. Results: Crude extract of H. helix(1-30 mg/kg) decreased blood pressure to greater extent in high salt-induced hypertensive rats in-vivo compared to the normotensive [Max. fall(58.59±0.02) mm Hg vs.(67.53±3.07) mmH g]. The n-hexane, chloroform, ethyl acetate and aqueous fractions were also checked. These fractions were more effective in hypertensive rats. Aqueous fraction was more potent and n-hexane the least. In isolated rat aortic rings precontracted with phenylephrine, crude extract induced endothelium-dependent effect. The endothelium-dependent component of vasodilatory effect was ablated with L-NAME, and denudation of endothelium. The aqueous fraction was most potent vasodilator. In aortic rings from hypertensive rats, extract and fractions produced partial endothelium-independent effect which was not affected by pretreatment with L-NAME, indicating endothelium dysfunction in the hypertensive rats and suggesting additional vasodilatory mechanisms. In rabbit aorta, the extract and fractions also inhibited phenylephrine and high K^+-induced precontractions, and shifted Ca^(++) concentration–response curves. Conclusions: Our findings indicate that extract and fractions of H. helix are antihypertensive remedies, which is the outcome of vasodilatory effect. This vasodilatory effect is mediated through ni

关键词： Hedera helix Antihypertensive Vasorelaxant Endothelium-dependent Nitric oxide calcium channel blocker

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calcium Signaling is Involved in Negative Phototropism of Rice Seminal Roots

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Rice science 2014年第1期21卷 39-46页

作者： CHEN Juan MO Yi-wei XU Hua-wei Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization College of Chemistry and Life Science Huanggang Normal University Institute of South Subtropical Crop Research Institute Chinese Academy of Tropical Agricultural Science College of Life Science Shaoxing University College of Agriculture Henan University of Science and Technology

calcium ions （Ca2＋） act as an intracellular second messenger and affect nearly all aspects of cellular life. They are functioned by interacting with polar auxin transport, and the negative phototropism of plant roots is caused by the transport of auxin from the irradiated side to the shaded side of the roots. To clarify the role of calcium signaling in the modulation of rice root negative phototropism, as well as the relationship between polar auxin transport and calcium signaling, calcium signaling reagents were used to treat rice seminal roots which were cultivated in hydroculture and unilaterally illuminated at an intensity of 100-200 pmol/（m2.s） for 24 h. Negative phototropism curvature and growth rate of rice roots were both promoted by exogenous CaCI2 lower than 100 pmol/L, but inhibited by calcium channel blockers （verapamil and LaCI3）, calcineurin inhibitor （chlorpromazine, CPZ）, and polar auxin transport inhibitor （N-l-naphthylphthalamic acid, NPA）. Roots stopped growing and negative phototropism disappeared when the concentrations increased to 100 pmol/L verapamil, 12.500 ~Jmol/L LaCI3, 60 pmol/L CPZ, and 6 pmol/L NPA. Moreover, 100 pmol/L CaCI2 could relieve the inhibition of LaCI3, verapamil and NPA. The enhanced negative phototropism curvature was caused by the transportation of more auxin from the irradiated side to the shaded side in the presence of exogenous Ca2＋. calcium signaling plays a key role as a second messenger in the process of light signal regulation of rice root growth and negative phototropism.

关键词： calcium signaling polar auxin transport calcium channel blocker second messenger negative phototropism

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Pharmacological Investigation of Voltage-dependent Ca^(2+) channels in Human Ejaculatory Sperm in vitro

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2006年第5期26卷 607-609页

作者：李路刘继红李家贵叶章群 Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

The types of the voltage-dependent calcium channels （VDCCs） in human ejaculatory sperm and the effects of calcium channel blocker （CCB） on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine （NIF, inhibitor of L-type VDCC） and ω-conotoxin （GVIA, inhibitor of N-type VDCC） were compared and analyzed statistically. The results showed that NIF （1, 5, 10 μmol/L） could not only significantly affect human sperm＇s shape but also spermatozoa motility after incubated at least 10 rain in vitro （P〈0.001）. GVIA （0.1, 0.5 and 1 μmol/L） could just only significantly affect human sperm＇s progressive motility （a %＋b %） after incubated for 20 min in vitro （P〈0.01）, but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.

关键词： voltage-dependent calcium channels calcium channel blocker human sperm motility in vitro

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ESTABLISHMENT OF K562/ADM/VER CELL SUBLINE RESISTANT TO VERAPAMIL AND ITS RESISTANT MECHANISM

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Chinese Journal of Cancer Research 2001年第2期13卷 115-118页

作者：谢佐福周冬梅林贤东林声吴允昆 Department of Immunopathology Fujian Province Tumor Hospital Fuzhou

Objective: To understand whether verapamil (VER) resistance development in the multidrug-resistant cell line and its mechanism. Methods: K562/ADM/VER cell subline resistant to verapamil was established through a gradual increase of VER concentration in the media. MTT method was used to assay resistance to VER, cross resistance to dipyriamole (DPM), cyclosporin A (CsA) in the cells, and HPLC and spectrofluorometer to detect intracellular accumulation of VER or ADM respectively, as well as S-P immunocytochemical technique for detection of genes expression. Results: It were observed that 7.9—fold increase in VER resistance, significantly reduced intracellular accumulation of VER or ADM and also develop across resistance to DPM and CsA in K562/ADM/VER cells, compared with its parent cell, K562/ADM. High-level of p-glycoprotein(pgp), middle-level of p53, p16, was present in two cell lines without expression of GSTPI, C-myc, C-myc, C-fos and C-erbB-2. Bc1–2 protein expression was found only in K562/ADM cells. Conclusion: K562/ADM cells were capable of being induced to develop resistance to VER.

关键词： Human leukemic cell experimental therapy Multidrug resistance calcium channel blocker Gene expression

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