AGTR1 A1166C gene polymorphism is associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension:A retrospective analysis

Objective:To investigate whether angiotensinⅡtype 1 receptor(AGTR1 A1166C)gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.Methods:This retrospective analysis included 198 patients(≥18 years of age)who received valsartan monotherapy(80 mg/day)for newly developed essential hypertension at the authors’center between January 1,2020 and December 31,2023.Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction(PCR)-melting curve analysis of genomic DNA from peripheral blood samples.A dominant genetic model for AGTR1 A1166C(AA genotype versus AC+CC genotype)was used.Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment(<140/90 mmHg)at the 4-week follow-up.Results:The median age of the 198 patients was(53.7±13.5)years,and 58%were men.Genotyping assays showed that 164 patients had the AA genotype,and 34 patients were of the AC/CC genotype,including 30 with the AC genotype and 4 with the CC genotype.Allele distribution was consistent with Hardy Weinberg equilibrium.109 Patients(55.1%)attained the blood pressure target.Multivariate analysis showed that smoking(versus no smoking,HR 0.314,95%CI 0.159-0.619,P=0.001)and AGTR1 A1166C AA genotype(versus AC/CC,HR 2.927,95%CI 1.296-6.611,P=0.023)were significant and independent predictors of target attainment.25 Patients(73.5%)with AGTR1 A1166C AC/CC genotype attained the target versus 51.2%(51/164)of patients with AGTR1 A1166C AA genotype(P=0.017).Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure[(33.1±10.8)mmHg versus(29.2±11.7)mmHg in AA carriers;(P=0.029)].Conclusions:Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.

Effect of Guanxin-V Mixture Combined with Sacubitril Valsartan on Cardiac Function after PCI in STEMI Patients

[Objectives]To observe the effect of Guanxin-V Mixture combined with Sacubitril Valsartan on cardiac function in patients after PCI for acute ST-segment elevation myocardial infarction(STE-MI).[Methods]41 cases of STEMI patients(qi and yin deficiency and blood stasis and obstruction)hospitalized in Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine from January 2020 to June 2021 were randomly divided into 21 cases in the treatment group and 20 cases in the control group,and the two groups were given standardized Western medicine treatment as soon as possible after PCI.The control group was treated with Sacubitril Valsartan,and the treatment group was treated with Guanxin-V Mixture on the basis of treatment in the control group.The patients in the two groups were treated for 3 months,and the TCM syndrome score,left ventricular ejection fraction(LVEF),and N-Terminal Pro-Brain Natriuretic Peptide(NT-proBNP),interleukin-6(IL-6),and high-sensitivity C-reactive protein(hs-CRP)levels,and the incidence of heart failure and adverse reactions in the two groups after treatment were recorded.[Results]After the treatment,the TCM syndrome score and serum NT-proBNP,IL-6 and hs-CRP levels of the two groups significantly decreased(P<0.05),and the levels of the treatment group were significantly lower than those of the control group(P<0.05);the LVEF of the two groups significantly increased(P<0.05),and the level of the treatment group was significantly higher than that of the control group(P<0.05).Comparison of the incidence of heart failure and adverse reactions in the two groups showed no statistically significant differences(P>0.05).[Conclusions]Guanxin-V Mixture combined with Sacubitril Valsartan could significantly improve cardiac function in STEMI patients undergoing PCI,and its effect may be related to the suppression of inflammatory response.

Evaluation of the Effectiveness and Efficiency of the Combination of Levamlodipine Besylate and Valsartan in the Treatment of Hypertension

Objective:To investigate the effectiveness and efficiency of combining levamlodipine besylate and valsartan in the treatment of hypertension.Methods:This study selected 28 patients with hypertension as observation subjects.The treatment duration ranged from January 2020 to June 2023.Using the random number table method,patients were divided into two groups.The control group received treatment with valsartan,while the observation group received a combination of valsartan and levamlodipine besylate.Therapeutic effects and safety were compared between the groups,and changes in the patient’s blood pressure and renal function index levels were assessed.Results:The total clinical effective rate of the observation group was significantly higher than that of the control group(P<0.05).The observation group demonstrated better diastolic blood pressure,systolic blood pressure,and renal function indicators compared to the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The combined treatment of levamlodipine besylate and valsartan in patients with hypertension showed significant clinical efficacy and holds broad application value.

Efficacy and safety of oral Chinese patent medicine combined with sacubitril/valsartan in the treatment of chronic heart failure:A Metaanalysis

Objective:To systematically evaluate the clinical efficacy of oral Chinese patent medicine combined with sacubitril/valsartan in treating chronic heart failure(CHF).Methods:CNKI,CSPD,CCD,CBM,PubMed,Web of Science,Cochrane Library and EMbase were retrieved to screen out randomized controlled trials Chinese patent medicine and Western medicine in treating CHF.Manual retrieval was also applied as a supplement.The Cochrane Reviewers Handbook 5.1.0 was used to evaluate the bias risk of the included studies and RevMan 5.4 software was used for Meta-analysis.Results:A total of 1301 patients enrolled in the 13 RCTs were included.According to the results of Meta-analysis,a combination of oral Chinese patent medicine and sacubitril/valsartan could further improve total effectiveness rate(RR=1.23,95%CI[1.16,1.30],P<0.001),increase 6 minutes’walk distance(MD=53.04,95%CI[33.43,72.64],P<0.001),improve left ventricular ejection fraction(MD=6.67,95%CI[5.15,8.19],P<0.001)and stroke volume(MD=7.56,95%CI[3.94,11.18],P<0.001),reduce left ventricular end-diastolic dimension(MD=-3.68,95%CI[-4.57,-2.78],P<0.001)and N terminal pro B type natriuretic peptide(MD=-434.08,95%CI[-518.95,-349.22],P<0.001)and no statistically significant difference in drug safety was found between the sacubitril/valsartan-only group and the combined treatment group(RR=0.73,95%CI[0.32,1.65],P=0.45).Conclusion:It’s indicated that a combination of traditional Chinese patent medicine and sacubitril/valsartan had a good clinical efficacy in the treatment of CHF,which had certain guiding significance for clinical practice.

Valsartan对糖尿病肾病肾保护作用的实验研究

目的 :探讨血管紧张素Ⅱ受体拮抗剂 (AT1RA)Valsartan对糖尿病大鼠肾脏基质金属蛋白酶 - 2 (MMP- 2 )及其抑制物 (TIMP - 2 )表达的影响。方法 :大鼠随机分为正常对照组 (A组 )、糖尿病组 (B组 )及治疗组 (C组 ) ,大鼠腹腔单剂量注射链脲佐菌素 (streptozotocin ,STZ) 6 5mg/kg建立糖尿病动物模型。治疗组给予Valsartan(缬沙坦 ) 10mg·kg-1·d-1灌胃。第 3周、第 6周各组分别宰杀 6只 ,检测肌酐清除率、尿白蛋白排泄率及肾重 /体重 ,免疫组织化学染色检测肾小球MMP - 2、TIMP - 2、纤维连接蛋白和Ⅳ型胶原表达。结果 :治疗组肌酐清除率 (P <0 .0 5 )、尿白蛋白排泄率 (P <0 .0 5 ,P <0 .0 1)及肾重 /体重 (P <0 .0 5 )均低于糖尿病组。免疫组织化学染色可见糖尿病大鼠肾小球TIMP - 2、纤维连接蛋白和Ⅳ型胶原表达明显增加 (P <0 .0 5 ,P <0 .0 1)。在治疗组 ,上述明显增加的表达均受到明显抑制 (P <0 .0 5 )。MMP - 2在糖尿病大鼠肾小球的表达明显被抑制 (P <0 .0 1) ,治疗组其表达明显增加 (P <0 .0 5 )。结论 :Valsartan通过上调糖尿病大鼠肾小球MMP - 2表达、下调TIMP - 2表达 ,对糖尿病大鼠肾脏病变有部分保护作用。

Valsartan对支架后新生内膜增生抑制作用的实验研究

目的 :再狭窄是血管内支架的主要并发症 ,缬沙坦 (Valsartan)作为新型的血管紧张素ⅡAT1 受体拮抗剂 ,可以特异阻断血管紧张素Ⅱ的促平滑肌分裂作用。本文通过动物实验来观察Valsartan对血管平滑肌细胞的抑制作用。方法 :2 0只兔 ,造成动脉硬化模型后 ,随机分成Valsartan组和对照组 ,采用超弹性镍钛合金自膨胀网状支架 ,通过股动脉植入兔的腹主动脉 ,血管造影测量狭窄程度 ,光镜下测量支架处血管新生内膜和中膜的厚度。结果 :2 0只兔共植入支架 2 0个 ,支架植入后即可及二个月血管造影 ,支架处无明显的狭窄 ;光镜下测量 :Valsartan组和对照组的新生内膜厚度分别为 194 2 4± 30 6 0um和 2 32± 33 0 2um ,P <0 0 1。中膜的厚度分别为 93 99± 14 75um和73 0 0± 17 78um ,P <0 0 5。结论 :Valsartan可以部分抑制支架后的平滑肌细胞增生 。

Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease

AIM： To assess whether treatment with insulinsensitizing agents （ISAs） in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet （MCDD） rat model of non-alcoholic fatty liver disease （NAFLD）. METHODS： Rats （n = 6 per group） were treated with different drugs, including MCDD only, MCDD diet with either metformin （200 mg/kg）, rosiglitazone （3 mg/kg）, metformin plus rosiglitazone （M＋R）, ezetimibe （2 mg/ kg）, valsartan （2 mg/kg）, or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured. RESULTS： Fatty liver （FL） rats demonstrated severe hepatic fatty infiltration （〉 91% fat）, with an increase in hepatic TG （＋1263%, P 〈 0.001）, hepatic cholesterol （＋245%, P 〈 0.03）, hepatic MDA levels （＋225%, P 〈 0.001）, serum TNF-alpha （17.8 ＋ 10 vs 7.8 ＋ 0.0, P 〈 0.001）, but a decrease in hepatic alpha tocopherol （-74%, P 〈 0.001） as compared to the control rats. Combination therapy with all drugs produced a significant decrease in liver steatosis （-54%）, hepatic TG （-64%）, hepatic cholesterol （-31%） and hepatic MDA （-70%）, but increased hepatic alpha tocopherol （＋443%） as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis （-32% vs -54%, P 〈 0.001） and in hepatic MDA levels （-55% vs -70%, P 〈 0.01）, but a similar decrease in hepatic lipids when compared with the all drugs combination. TNF-alpha levels decreased significantly in all treatment groups except in ISA group. CONCLUSION： Combination therapies have a greater effect on liver fat content as compared to monotherapy. Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin.

Simultaneous determination of amlodipine,valsartan and hydrochlorothiazide by LC-ESIMS/MS and its application to pharmacokinetics in rats

Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.

A simple and efficient synthesis of the valsartan

Valsartan 1, one of the most important agents used in antihypertensive therapy today, was synthesized starting from L-valin methyl ester hydrochloride 2 through four steps in an overall yield of 60%. The key step involves the palladium-catalyzed Suzuki coupling. This method overcomes many of the drawbacks associated with the previously reported syntheses and is more suitable for industrial production.

Efficacy and safety of valsartan plus hydroclorothiazide for high blood pressure

AIM:To evaluate efficacy and tolerability of the combination valsartan plus hydrochlorothiazide(160 mg and 25 mg daily,respectively) in young-middle aged males with high-normal blood pressure(BP) or firstdegree arterial hypertension with evidence of target organ damage.METHODS:Twenty males with high-normal BP or first-degree hypertension associated with left ventricular concentric remodeling and/or increased aortic stiffness were enrolled.BP at rest and during exercise,and echocardiographic parameters of the left ventricle(LV),were evaluated at baseline and after 3 mo of treatment.The effects of treatment on aortic stiffness,metabolic parameters,renal and erectile function were also assessed.RESULTS:BP was significantly reduced by treatment both at rest(P < 0.001) and during exercise(P < 0.001),and 85% of patients achieved BP normalization(< 130/85 mmHg).Doppler echocardiography showed a significant reduction of LV mass(P < 0.005).LV hypertrophy was identified in 70% of subjects at baseline and in 5% after 3 mo of treatment.The ratio of early(E) to late(A) trans-mitral diastolic flow velocity increased,(P < 0.05),the relative wall thickness decreased(P < 0.05) and the left ventricular relaxation time shortened(P < 0.005).The left atrial diameter(P < 0.05) and the aortic diameter(P < 0.05) and stiffness(P < 0.005) also decreased.CONCLUSION:The full-dose combination of valsartan plus hydrochlorothiazide produced optimal BP control with regression of target organ damage,already after 3 mo,without relevant side effects.

Application of an LC–MS/MS method for the analysis of amlodipine,valsartan and hydrochlorothiazide in polypill for a bioequivalence study

A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.

Valsartan Inhibits Angiotensin Ⅱ-induced Proliferation of Vascular Smooth Muscle Cells via Regulating the Expression of Mitofusin 2

Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGⅡ by cell counting and methyl thiazolyl tetrazolium (MTT) assay,and detected the expression of mitofusin 2 (Mfn2),a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway pro-tein by Western blotting.ANGⅡ at a concentration of 10-6 mol/L significantly stimulated VSMCs proliferation,down-regulated the expression of Mfn2 and upregulated the expression of Raf and ERK1/2.Valsartan inhibited such effects of ANGⅡ at concentrations of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no significant effect on the proliferation of untreated VSMCs.These results suggest that valsartan inhibits ANGⅡ-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.

Changing the treatment of heart failure with reduced ejection fraction： clinical use of sacubitril-valsartan combination

Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor （ARNI） since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides （NPs）, bradykinin, endothelin and angiotensin II （Ang-II）. Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ （with opposite biological actions）. So, a combined inhibition of these both systems （Sacubitril / valsartan） may enhance the benefits of NPs effects in HF （natriuresis, diuresis, etc） while Ang-Ⅱ receptor is inhibited （reducing vasoconstriction and aldosterone release）. In a large clinical trial （PARADIGM-HF with 8442 patients）, this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF （compared to enalapril）. This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.

Valsartan延缓血管内皮细胞衰老及p16^(INK4a)表达变化的研究

目的探讨Valsartan对血管内皮细胞衰老与p16INK4a表达变化的影响,为寻求延缓内皮细胞衰老途径提供理论和实验依据。方法体外培养人脐静脉内皮细胞,予血管紧张素Ⅱ及Valsartan干预,实验分为空白对照组、血管紧张素Ⅱ诱导组及Valsartan组,采用β-半乳糖苷酶(β-gal)染色鉴定细胞衰老;流式细胞术分析细胞周期变化;免疫细胞化学染色法、Western blot分析各组细胞p16INK4a蛋白的表达。结果与对照组比较,血管紧张素Ⅱ诱导组β-半乳糖苷酶阳性染色率显著增多81.24%±6.46%,细胞周期停滞于G0-G1(88.36%±6.45%),p16INK4a蛋白表达水平上调(P<0.05);予以Valsartan干预后,β-半乳糖苷酶阳性细胞染色率减少,G0-G1细胞减少,p16INK4a蛋白表达水平下调(P<0.05)。结论血管内皮细胞衰老分子机制可能通过下调p16INK4a的表达,使细胞周期停滞于G1期有关,Valsartan对血管内皮细胞衰老有一定保护作用,可能通过调控p16INK4a的表达发挥其延缓3血管内皮细胞衰老的作用。

Preparation and characterization of spray-dried valsartan-loaded Eudragit~? EPO solid dispersion microparticles

The purpose of this study was to develop the immediate release stomach-specific spraydried formulation of valsartan(VAL) using Eudragit?E PO(EPO) as the carrier for enhancing dissolution rate in a gastric environment. Enhanced solubility and dissolution in gastric pH was achieved by formulating the solid dispersion using a spray drying technique. Different combinations of drug–polymer–surfactant were dissolved in 10% ethanol solution and spraydried in order to obtain solid dispersion microparticles. Use of the VAL–EPO solid dispersion microparticles resulted in significant improvement of the dissolution rate of the drug at pH 1.2 and pH 4.0, compared to the free drug powder and the commercial product. A hard gelatin capsule was filled with the VAL–EPO solid dispersion powder prior to the dissolution test.The increased dissolution of VAL from solid dispersion microparticles in gastric pH was attributed to the effect of EPO and most importantly the transformation of crystalline drugs to amorphous solid dispersion powder, which was clearly shown by scanning electron microscopy(SEM), differential scanning calorimetry(DSC), and powder X-ray diffraction(PXRD) studies. Thus, VAL, a potential antihypertensive drug in the form of a solid dispersion microparticulate powder, can be effectively delivered in the immediate release dosage form for stomach-specific drug delivery.

Clinical Utility of Amlodipine/Valsartan Fixed-Dose Combination in the Management of Hypertension in Chinese Patients

Amlodipine/valsartan(Aml/Val)single-pill combination(SPC)therapy has been widely used and studied in clinical practice in recent years.This article reviews the Chinese and English literature on the clinical use of Aml/Val SPC therapy in Chinese hypertensive patients.According to five studies concerning the efficacy and safety of this treatment,Aml/Val SPC therapy was more efficacious than monotherapy with valsartan,amlodipine,or the nifedipine gastrointestinal therapeutic system.This treatment showed greater blood pressure-lowering effects,a higher blood pressure control rate,and a higher response rate.Aml/Val SPC treatment was well tolerated,with adverse event rates similar to those of monotherapy with valsartan or amlodipine and significantly rarer adverse events compared with the nifedipine gastrointestinal therapeutic system.Aml/Val SPC is a highly efficacious and well-tolerated antihypertensive treatment in Chinese hypertensive patients.

Recurrent hypotension induced by sacubitril/valsartan in cardiomyopathy secondary to Duchenne muscular dystrophy: A case report

BACKGROUND Duchenne muscular dystrophy(DMD),which is caused by a mutation/deletion in the dystrophin gene on the X-chromosome,is the most common type of neuromuscular disorder in pediatrics.Skeletal muscle weakness progressively develops in DMD patients and usually leads to respiratory failure in the early adolescent years.Cardiac muscle is frequently affected in DMD patients,which leads to a high burden of cardiomyopathy and heart failure.In the era of improved respiratory care,cardiac deaths are becoming the major cause of mortality in DMD patients.CASE SUMMARY We report the case of a 15-year-old boy who presented to the hospital due to recurrent orthopnea for 6 mo and palpitations for 4 mo.He was diagnosed with progressive muscular dystrophy at the age of 3 years and was confined to a wheelchair at 12 years.He was prescribed diuretics and digoxin at the outpatient clinic;however,his symptoms did not resolve.Sacubitril/valsartan was added 1 mo prior to presentation,but he experienced recurrent episodes of palpitations.The electrocardiogram showed atrial tachycardia with a heart rate of 201 bpm,and he was then hospitalized.Hypotension was found following the administration of sacubitril/valsartan tablets;he could not tolerate even a small dose,always developing tachyarrhythmia.His symptoms were relieved after discontinuing sacubitril/valsartan,and his heart rate was controlled by a small dose of metoprolol tartrate and digoxin.Atrial tachycardia spontaneously converted in this patient,and his symptoms attenuated in the following 6 mo,without palpitation episodes.CONCLUSION Blood pressure should be closely monitored in DMD patients with advanced heart failure when taking sacubitril/valsartan.

After having changed the treatment of heart failure with reduced ejection fraction: what are the latest evidences with sacubitril valsartan?

1 Introduction Sacubitril/valsartan(SV)is a first in class dual action molecule of the neprilysin(NEP)inhibitor prodrug sacubitril(AHU377)and the angiotensin II receptor(Ang-II)type 1 antagonist valsartanJ11 It is the first angiotensin receptor-neprilysin inhibitor(ARNI)whose pharmacodynamic effects are consistent with a simultaneous stimulation of the natriuretic peptides system(via NEP inhibition)and the blockade of the renin-angiotensin-aldosterone system(valsartan effect)that finally results in systemic vasodilation,increased diuresis and natriuresis,reduction of plasmatic volume and diminution of peripheral vascular resistance.

Effects of the Combined Use of Benazepril and Valsartan on Apoptosis in the Kidney of Rats with Adriamycin-induced Nephritic Glomerulosclerosis

Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.

口服缬沙坦(Valsartan)前后阴茎海绵体血液生化研究

目的 :通过阴茎海绵体血生化指标的检测 ,探索缬沙坦 (Valsartan)在阴茎海棉体平滑肌中的作用。方法 :选取 5 6例勃起功能障碍病人 ,给予缬沙坦口服两个月 ,前后血气分析及血 No含量测定 ,所有病例均分为 1)前列腺素E1 尿道给药 +缬沙坦 (n=15 ) ,2 )安慰剂 +缬沙坦 (n=2 0 ,3)前列腺素 E1 尿道给药 +安慰剂 (n=2 1)三组进行对比。结果 :(1)三组病人阴茎海绵体血液 No含量接受实验前后均有明显变化 ,而前列腺素 E1 尿道给药 +缬沙坦组作用效果优于其他两组。 (2 )血气分析方面 :两种药物使用前后对比 ,PO2 及 O2 Sat均存在显著性差异 ;前列腺素 E1 尿道给药+安慰剂 ,安慰剂 +缬沙坦使用前后 p H值无显著差异 ,而前列腺素 E1 尿道给药 +缬沙坦 ,前后有显著性差异 ,而这两种制剂效果之间相比 ,p H,PO2 值之间存在显著性差异 ,O2 Sat值之间无显著性差异。结论 :前列腺素 E1 尿道给药 +缬沙坦联合使用可成为一良好的 No供体 ,而 No可导致阴茎海绵体平滑肌舒张 ,血流增加 。