Effect of microparticles derived from bone marrow mesenchymal stem cells on cardiomyocyte hypertrophy and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of microparticles(MPs)derived from bone marrow mesenchymal stem cells(BMSCs) on myocardial hypertrophy and its mechanism.Methods The osteogenic differentiation and adipogenic differentiation of mesenchymal stem cells(MSCs) were induced. After isolation and purification,the morphological characteristics were observed by transmission electron microscope,and the MPs surface antigen was identified by flow cytometry. Myocardial hypertrophy model was induced by using isoprenaline(ISO)in rats,which were measured for the cardiac structure and function by echocardiography,and then detected for various indexes of the heart and isolated left ventricle. Single ventricular myocytes of rats were acutely isolated and divided into control group(Control group),cardiomyocyte hypertrophy group(ISO group),MPs group(MPs group),and MPs supernatant group(Supernatant group). The mRNA expressions of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)were detected by qRTPCR. The expression levels of calmodulin-dependent protein kinaseⅡ（CaMKⅡ）and phosphorylated calmodulin-dependent protein kinaseⅡ（p-CaMKⅡ）were detected by ELISA. The L-type calcium current(LCa-L)in single ventricular myocyte of various groups was recorded by whole-cell patch clamp.Results The bone nodules of MSCs osteogenic differentiation turned red after alizarin red staining,and lipid droplets of adipogenic differentiation turned red after oil red O staining;Under transmission electron microscope,MPs membrane had a complete structure,a clear outline and a diameter of about200 nm;The positive rates of CD29 and CD90 on the surface of MPs were(98. 24 ± 0. 82)% and(97. 69 ± 1. 83)%,respectively. Compared with Control group,the left ventricular end diastolic dimension(LVEDD)reduced signifi-cantly(t =5. 065,P < 0. 05),while the interventricular septum end-diastolic dimension(IVSd),left ventricular posterior wall dimension(LVPWd),heart weight to body weight ratio(HW/BW),and heart weight to tibial length ratio(HW/Tibia)significantly increased in ISO group(t = 4. 013,2. 368,4. 392,5. 043 and 6. 120,respectively,each P < 0. 05),indicating that the hypertrophic model was successfully established. The expression levels of ANP and BNP mRNA in hypertrophic cardiomyocytes of rats in ISO group were significantly higher than those in Control group(t = 25. 120 and18. 261,respectively,each P < 0. 01);While the expression levels of ANP and BNP mRNA in MPs group significantly reduced after incubation with 48 μg/mL MPs for 48 h compared with ISO group(t = 12. 110 and 3. 526,respectively,each P < 0. 05);The expression levels of CaMK Ⅱand p-CaMKⅡ in ISO group were significantly higher than those in Control group(t = 3. 278 and 4. 181,respectively,each P < 0. 05),while the expression of p-CaMK Ⅱ in MPs group decreased significantly(t = 5. 420,P < 0. 05);The calcium current density in ISO group was significantly higher than that in Control group(t = 15. 261,P < 0. 01),while that in MPs group was significantly lower than that in ISO group(t =6. 216,P < 0. 05).Conclusion MSC-MPs can significantly inhibit ISO-induced cardiomyocyte hypertrophy in rats,which is related to its down-regulation of cardiomyocyte CaMKⅡ and inhibition of L-type calcium channel.

Research progress of TRPV4 in ocular pathophysiological function / 国际眼科杂志(Guoji Yanke Zazhi)

Transient receptor potential vanilloid receptor 4(TRPV4)is a non-selective cation channel responsible for sensing changes in cell swelling, temperature, mechanical stretch, shear stress and osmotic pressure by regulating transmembrane calcium signaling and thereby influencing gene expression, cell morphology, and cytoskeletal construction. TRPV4 is widely expressed throughout the body. Intraocularly, TRPV4 is functionally expressed in the cornea, lens, ciliary body, trabecular meshwork and retina. In this article, the expression and physiopathological functions of TRPV4 in various tissues of the eye were described. With the in-depth study of TRPV4 in ocular pathophysiological functions, TRPV4 may become a potential drug target in corneal injury repair, glaucoma and retinal angiogenesis, but further in-depth study is still needed.

Slow-flow phenomenon after drug-coated balloon angioplasty for lower-extremity arteries is associated with lack of prescribing of calcium channel blockers

This study aimed to investigate the relationship between prescription drugs and the slow-flow phenomenon after drug-coated balloon angioplasty. Of 30 patients, five (17%) presented with the slow-flow phenomenon. Patients with the slow-flow phenomenon were significantly less commonly prescribed calcium channel blockers than those without the slow-flow phenomenon (P ¼ 0.03). There was no intergroup difference in the prescription of angiotensin II receptor blockers and b-blockers. The clinical outcomes, including restenosis, thrombosis, target lesion revascularization, and death, did not differ between groups during the 10-month observation period.

Efficacy and Safety of Fixed-Dose Combination of Efonidipine and Telmisartan in Stage II Hypertensive Patients: Results from Randomized Clinical Trial

Aim: The aim of this study was to evaluate the anti-hypertensive efficacy of a fixed-dose combination (FDC) of Efonidipine 40 mg and Telmisartan 40 mg in Stage II hypertensive patients. Study Design: Multicentric, randomized, double-blind, parallel, comparative Phase III clinical trial. Methodology: This clinical trial was conducted at six geographically distributed sites across India and enrolled 240 Stage II hypertensive patients. They were randomized into two groups in a ratio of 1:1 using computer-generated block randomization to receive E+T (FDC of Efonidipine 40 mg + Telmisartan 40mg) or C+T (FDC of Cilnidipine 10 mg + Telmisartan 40 mg) group intervention once daily for a period of 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study evaluated the mean reduction in sitting systolic BP (SBP) and diastolic BP (DBP) from baseline to day 90 whereas the secondary endpoints assessed were mean reduction in BP from baseline to day 30 & 60, patients achieving target BP (<140/90 mmHg) and the safety and tolerability of the investigational products based on the incidences of adverse events (AEs) reported. Results: A total of 118 subjects were randomized to the E+T group wherein the mean (±SD) SBP and DBP at baseline was 167.25 ± 4.68/107.26 ± 5.19 mmHg. After 30 days of treatment with the E+T group, the mean reduction in SBP/DBP of 29.37/18.06 mmHg was observed whereas at Day 60 reduction of 38.55/22.69 mmHg was seen from the baseline. At Day 90, SBP/DBP decreased to 119.41±14.99/81.67±4.29 mmHg with a mean reduction of 47.94/25.89 mmHg in the E+T group. During the study period, the difference in systolic blood pressure between the treatments with E+T and C+T was -0.48 mmHg, with the two-sided 95% confidence interval (CI) ranging from -4.54 to 3.58?mmHg. The corresponding difference in diastolic blood pressure was -0.77 (95% CI: -2.60 to 1.06) mm?Hg. The upper boundary of the 95% CI was below the margin of 10?mmHg, confirming the non-inferiority of E+T to C+T. A total of 92% of patients who had been assigned to E+T treatment achieved their target BP goal. Only one patient reported an adverse event with E+T treatment. No unexpected AEs were reported in the E+T group suggesting its good safety and tolerability. Overall, the E+T treatment was effective, safe and well-tolerated by the patients for 90 days. Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Telmisartan 40 mg was efficacious in the management of Stage II hypertension.

Advances in Medical Treatment of Primary Aldosteronism / 中国医学科学杂志(英文版)

Primary aldosteronism (PA) is the most common form of secondary hypertension, with its main manifestations including hypertension and hypokalemia. Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction. The past decade has witnessed the rapid advances in the genetics of PA, which has shed new light on PA treatment. While surgery is the first choice for unilateral diseases, bilateral lesions can be treated with mineralocorticoid receptor antagonists (MRAs). The next-generation non-steroidal MRAs are under investigations. New medications including calcium channel blockers, macrophage antibiotics, and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Mechanism of the therapeutic effect of Tetrandrine on striatum injury caused by microwave radiation / 中华放射医学与防护杂志

Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.

Developmental epileptic encephalopathy associated with the CACNA1E gene mutation / 中华实用儿科临床杂志

One of the important causes of developmental epileptic encephalopathy (DEE) is the mutation of ion channel genes, including the mutation of the CACNA1E gene. CACNA1E-related DEE cases were first reported in 2018.The mutation types include new missense mutations, nonsense mutations and frameshift mutations, but the correlation between mutation sites and types with the phenotype of DEE is not clear.This review aims to summarize the reported CACNA1E-related DEE cases, and explore the correlation between the clinical phenotype of CACNA1E-related DEE and gene mutation sites and mutation types.Meanwhile, possible pathogenesis of CACNA1E-related DEE and the progress of drug intervention were reviewed to provide references for the diagnosis and precise treatment of DEE.

Research progress of voltage-gated Calcium channel gene mutations associated with epilepsy in children / 中华实用儿科临床杂志

Abnormal expression and dysfunction of voltage-gated Calcium channels (VGCCs) can give rise to a variety of neurological disorders in children, including epilepsy, migraine and ataxia.In the past, only CACNA1A, CACNA1H, CACNA2D2 and CACNB4 were considered associated with epilepsy in children.In recent years, an increasing number of VGCCs gene associated with epilepsy in children have been found, especially developmental and epileptic encephalopathy genes.This study aims to review the research progress of VGCCs gene mutations associated with epilepsy in children.

Calcium/Calmodulin Mediates Cardiomyocyte Ferroptosis in Myocardial Infarction Through Iron Overload / 中国生物化学与分子生物学报

Myocardial infarction(MI), an acute coronary syndrome that poses a serious risk to human health, involves multiple pathophysiological processes, including calcium overload. Existing therapeutic approaches and preventive measures have limitations and cannot effectively repair myocardial cells with poor regenerative potential. Exploring multiple programmed modes of cardiomyocyte death could help find potential targets for the treatment of myocardial infarction, and the potential role of ferroptosis as a novel mode of cell death in myocardial infarction has attracted great attention. The aim of this study was to investigate whether Ca

The Role of Post-Translational Modifications of Cav3. 2 in Neuropathic Pain / 中国生物化学与分子生物学报

Neuropathic pain is a common chronic pain that affects human health worldwide. As an important mediator of excitatory conduction in neurons, ion channels are important targets for mechanism research and drug research in this field. T-type calcium channel(Cav3) can be activated transiently when neurons are close to the resting potential of -70 mV, resulting in a transient Ca

Effect of menthol, a transient receptor potential melastatin-8 channel activator, on pulmonary arterial hypertensive rats / 中国药理学通报

Aim To investigate the effects of menthol, a transient receptor potential melastatin-8 channel activator, on treating pulmonary arterial hypertension (PAH) in PAH model rats caused by monocrotaline (MCT). Methods Male Sprague-Dawley rats were divided into six groups randomly (control group, MCT group, MCT + menthol 1 mg • kg

Rho A/ROCK signaling pathway involved in hyper responsiveness to aortic contraction in mice with type 2 diabetes / 中国药理学通报

Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl

Analysis of genes related to female bone peak and osteoporosis based on bioinformatics / 中国骨伤

OBJECTIVE@#To explore and verify the genes related to female peak bone mass(PBM) and osteoporosis (OP) based on bioinformatics.@*METHODS@#Using GEO data, DNA microarray technology to conduct genome-wide analysis of adult female monocytes with high and low PBM. Cluster analysis, GO enrichment and KEGG analysis were used to analyze the differential genes, and the interaction network of differential genes was further analyzed. OP rat model was established and femur neck tissue staining was performed to further verify the expression of differential genes.@*RESULTS@#A total of 283 genes were obtained by differential gene screening. Compared with the high PBM samples, 135 genes were up-regulated and 148 genes were down-regulated in the low PBM samples. A total of 7 pathways and 12 differential genes were enriched, and there were differences in the expression of several genes involved in mineral absorption and transport, cellular immunity and other aspects. Among them, voltage-gated Ca2+ channel 1.3(CaV1.3) encoded by CACNA1D gene was significantly enhanced in the femoral neck tissue of OP rat model.@*CONCLUSION@#The above results suggest that the difference in the expression level of CaV1.3 gene may lead to the occurrence of OP in women with low PBM, which provides us with a potential target for the prevention and treatment of OP.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension / Perda de resposta a bloqueadores dos canais de cálcio após acompanhamento prolongado em pacientes com hipertensão arterial pulmonar idiopática

ABSTRACT Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

RESUMO Pacientes com hipertensão arterial pulmonar (HAP) idiopática com resposta positiva ao teste de vasorreatividade aguda e resposta clínica a bloqueadores dos canais de cálcio (BCC) durante no mínimo um ano são tradicionalmente denominados "respondedores verdadeiros". No entanto, pouco se sabe sobre a manutenção da resposta a BCC durante períodos mais longos. Avaliamos a perda de resposta a BCC após tratamento prolongado em uma coorte de pacientes com HAP idiopática previamente considerados respondedores verdadeiros. Nossos dados sugerem que pacientes com HAP idiopática podem deixar de apresentar resposta clínica a BCC mesmo depois de um ano de estabilidade clínica, reforçando a necessidade de reavaliação multidimensional constante para avaliar a necessidade de terapias específicas para HAP e classificar esses pacientes corretamente.

Study of central aortic blood pressure in hypertensive patients & its relation with blood pressure-lowering drugs

Background & objectives: In clinical settings, peripheral blood pressure (PBP) is measured routinely. It is thought that central blood pressure (CBP) which reflects aortic BP, may be more predictive of outcomes in specific populations. Hence, this study was carried out to measure CBP in patients with hypertension and to see the effect of antihypertensive drugs on CBP. Methods: This cross-sectional study was conducted on 134 hypertensive patients and 134 normotensive healthy individuals as controls. Peripheral BPs and CBPs were measured of all patients and controls. The data were correlated and the effect of antihypertensive drugs on CBP was also evaluated. Results: Of the 134 hypertensive patients, 44 (32.84%) were newly diagnosed and the rest 90 (67.16%) had a history of hypertension and were on treatment. Of these 90 patients on treatment, 37 (41.11%) had uncontrolled peripheral BP and 53 (58.89%) had normal peripheral BP. Of the 134 hypertensive patients, 45 (33.58%) had controlled CBP. In 90 patients, who were on antihypertensive treatment, 45 (50%) had controlled CBP and 45 (50%) had uncontrolled CBP. Patients on calcium channel blockers (CCBs) had better control of CBP. Interpretation & conclusions: Hypertension is diagnosed mainly by measuring peripheral BP. CBP, which correlates better with the incidence of cardiovascular events, is not routinely measured. Patients with a history of hypertension and on treatment had normal office peripheral BP, but a few of them had high CBP and may require modification in treatment for control of CBP. Control of CBP was better in patients taking CCB.

Mibefradil improves skeletal muscle mass, function and structure in obese mice / 南方医科大学学报

OBJECTIVE@#To observe the effect of mibefradil on skeletal muscle mass, function and structure in obese mice.@*METHODS@#Fifteen 6-week-old C57BL/6 mice were randomized equally into normal diet group (control group), high-fat diet (HFD) group and high-fat diet +mibefradil intervention group (HFD +Mibe group). The grip strength of the mice was measured using an electronic grip strength meter, and the muscle content of the hindlimb was analyzed by X-ray absorptiometry (DXA). Triglyceride (TG) and total cholesterol (TC) levels of the mice were measured with GPO-PAP method. The cross-sectional area of the muscle fibers was observed with HE staining. The changes in the level of autophagy in the muscles were detected by Western blotting and immunofluorescence assay, and the activation of the Akt/mTOR signaling pathway was detected with Western blotting.@*RESULTS@#Compared with those in the control group, the mice in HFD group had a significantly greater body weight, lower relative grip strength, smaller average cross sectional area of the muscle fibers, and a lower hindlimb muscle ratio (P < 0.05). Immunofluorescence assay revealed a homogenous distribution of LC3 emitting light red fluorescence in the cytoplasm in the muscle cells in HFD group and HFD+Mibe group, while bright spots of red fluorescence were detected in HFD group. In HFD group, the muscular tissues of the mice showed an increased expression level of LC3 II protein with lowered expressions of p62 protein and phosphorylated AKT and mTOR (P < 0.05). Mibefradil treatment significantly reduced body weight of the mice, lowered the expression level of p62 protein, and increased forelimb grip strength, hindlimb muscle ratio, cross-sectional area of the muscle fibers, and the expression levels of LC3 II protein and phosphorylated AKT and mTOR (P < 0.05).@*CONCLUSION@#Mibefradil treatment can moderate high-fat diet-induced weight gain and improve muscle mass and function in obese mice possibly by activating AKT/mTOR signal pathway to improve lipid metabolism and inhibit obesityinduced autophagy.

Nicardipine versus nitroglycerin for hypertensive acute heart failure syndrome: a single-center observational study / Journal of Rural Medicine

Objective: Nitroglycerin is a first-line treatment for hypertensive acute heart failure syndrome (AHFS). However, nicardipine is frequently used to treat hypertensive emergencies, including AHFS. In this study, we compared the effectiveness of nicardipine and nitroglycerin in patients with hypertensive AHFS.Patients and Methods: This single-center, retrospective, observational study was conducted at the intensive care unit of a Japanese hospital. Patients diagnosed with AHFS and systolic blood pressure 140 mmHg on arrival between April 2013 and March 2021 were included. The outcomes were the time to optimal blood pressure control, duration of continuous infusion of antihypertensive agents, duration of positive pressure ventilation, need for additional antihypertensive agents, length of hospital stay, and body weight changes. Outcomes were compared between the nicardipine and nitroglycerin groups. We also compared these outcomes between the groups after excluding patients who received renal replacement therapy.Results: Fifty-eight patients were enrolled (26 and 32 patients were treated with nitroglycerin and nicardipine, respectively). The nicardipine group had a shorter time to optimal blood pressure control (2.0 [interquartile range, 2.0–8.5] h vs. 1.0 [0.5–2.0] h), shorter duration of continuous anti-hypertensive agent infusion (3.0 [2.0–5.0] days vs. 2.0 [1.0–2.0] days), less frequent need for additional anti-hypertensive agents (1 patients [3.1%] vs. 11 patients [42.3%]), and shorter length of hospital stay (17.5 [10.0–33.0] days vs. 9.0 [5.0–15.0] days) than the nitroglycerin group. The duration of positive pressure ventilation and body weight changes were similar between the groups. The outcomes were similar after excluding patients who received renal replacement therapy.Conclusion: Nicardipine may be more effective than nitroglycerin for treating hypertensive AHFS.

Effects of antihypertensive drugs on renal function after percutaneous transluminal coronary angioplasty / 药学实践杂志

Objective To evaluate the effects of antihypertensive drugs on renal function after percutaneous transluminal coronary angioplasty. Methods A retrospective analysis was performed on 193 patients who underwent percutaneous transluminal coronary angioplasty and took antihypertensive drugs regularly. Those patients were admitted to Nanjing Drum Tower Hospital during January 2020 to December 2020. The patients were divided into ACEI/ARB group, β-blockers, calcium channel blockers and hydration control group. All patients received routine hydration during the perioperative period. The changes of serum creatinine (Scr), blood urea nitrogen (BUN), estimated glomerular filtration rate(eGFR) and endogenous creatinine clearance rate (Ccr) before and after operation were compared. Results The incidence of CIN was 0% in four groups. Compared with the preoperative, there was no significant change in Scr and Ccr in every group. Except for the hydration control group, the BUN levels in three treated groups were reduced after postoperative. Specifically, the BUN reduction in β-blockers group has statistically significant difference compared to the hydration control group and CCB group. In addition, eGFR levels were significantly reduced in the β-blockers group. Preoperative Scr and Ccr levels in patients with high blood pressure (SBP≥140 or DBP≥90) were significantly different from the patients with normal blood pressure (SBP<140 and DBP<90). Conclusion The use of ACEI/ARB and CCB before percutaneous transluminal coronary angioplasty had no effect on renal function in the short term. β-blockers can slightly reduce renal function, especially in patients with high blood pressure, who should receive special attention.

Individualized precision therapy for patients with ischemic stroke and hypertension / 中国临床药理学与治疗学

AIM: To investigate the influence of CYP3A5 gene polymorphism on the anti-hypertensive efficacy of calcium channel blocker in patients with ischemic stroke and hypertension. METHODS: A total of 108 cases of ischemic stroke patients with hypertension were included and divided into experimental group and control group, and 54 cases in each group, the experimental group selected amlodipine tablets and levamlodipine tablets respectively according to the results of genetic testing, while the control group selected amlodipine tablets, which in order to investigate the antihypertensive efficacy of the two groups. RESULTS: The effective rate of experimental group and control group was 77.78% and 57.41% (P 0.05). In the experimental group, the antihypertensive effect of GG and AG genotype patients after taking amlodipine tablets was significantly higher than that of AA type patients, and GG type patients had a stronger antihypertensive effect than AG type patients after taking amlodipine tablets. CONCLUSION: CYP3A5 gene polymorphism is very important for blood pressure control by calcium channel blockers in patients with ischemic stroke and hypertension.

Role of calcium-independent phospholipase A2 in contraction of intrarenal artery smooth muscle / 中国药理学通报

Aim To investigate the role of calcium-independent phospholipase A2(iPLA2)in calcium regu-lation of intrarenal artery smooth muscle contraction.Methods The method of measuring the tension of isolated arterioles was used to explore the effect of bromoenol lactone(BEL), a specific inhibitor of iPLA2, on the tension of the intrarenal arteries in mice induced by different calcium channels, and the laser confocal calcium measurement technology was used to investigate the effect of BEL on the intracellular calcium influx mediated by arachidonic acid-mediated calcium channels.Results The intrarenal artery concentration dependent contractile response induced by the vasoconstrictors phenylephrine and 5-hydroxy tryptamine was inhibited by BEL(P<0.01).The contraction curve induced by CaCl2 was also inhibited by BEL(P<0.05).In the calcium-free K-H solution incubated with nifedipine, the intrarenal artery vasoconstriction caused by the release of sarcoplasmic reticulum calcium and the calcium influx of the SOC channel induced by CaCl2 was inhibited by BEL(P<0.05).BEL significantly inhibited the external calcium influx mediated by the ARC channel of human aortic smooth muscle cell lines incubated with nifedipine(P<0.01).Conclusions iPLA2 mediates the contractile response of intrarenal arteries by regulating the functions of L-type calcium channels, sarcoplasmic reticulum calcium release, SOC channels and ARC channels.