Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

Renin-angiotensin system blockers-SGLT2 inhibitorsmineralocorticoid receptor antagonists in diabetic kidney disease:A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease(DKD)have been tested in patients with type 2 diabetes mellitus(T2DM)in the past two decades.With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001,no other pharmacological agent tested in the past two decades have shown any clinically meaningful result.Recently,the sodium-glucose cotransporter-2 inhibitor(SGLT-2i),canagliflozin,has shown a significant reduction in the composite of hard renal and cardiovascular(CV)endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of reninangiotensin system blocker use.Another SGLT-2i,dapagliflozin,has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease(CKD),regardless of T2DM status.Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM.However,the full results of this trial have not yet been published.While the use of older steroidal mineralocorticoid receptor antagonists(MRAs)such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes,a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM,with reasonably acceptable side effects.

Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the mortality in sepsis: A meta-analysis

BACKGROUND The effect of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin receptor blockers(ARBs)on the mortality of patients with sepsis is not well characterized.AIM To elucidate the association between prior ACEI or ARB exposure and mortality in sepsis.METHODS The PubMed,EMBASE,Web of Science,and Cochrane Library databases were searched for all studies of premorbid ACEI or ARB use and sepsis mortality until November 302019.Two reviewers independently assessed,selected,and ab-stracted data from studies reporting ACEIs or ARBs,sepsis,and mortality.The primary extracted data consisted of premorbid ACEI or ARB exposure,mortality,and general patient data.Two reviewers independently assessed the risk of bias and quality of evidence.RESULTS A total of six studies comprising 281238 patients with sepsis,including 49799 cases with premorbid ACEI or ARB exposure were eligible for analysis.Pre-morbid ACEIs or ARBs exposure decreased the 30-d mortality in patients with sepsis.Moreover,the use of ACEIs or ARBs was associated with approximately a 6%decreased risk of 30-d mortality.CONCLUSION The results of this systematic review suggest that ACEI or ARB exposure prior to sepsis may be associated with reduced mortality.Further high-quality cohort studies and molecular mechanism experiments are required to confirm our results.

Proton pump inhibitors therapy vs H_2 receptor antagonists therapy for upper gastrointestinal bleeding after endoscopy: A meta-analysis

AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and Pub Med for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios(OR) and mean difference with 95% confidence interval(CI). Rev Man 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors(PPI) group and the remaining 605 subjects were in the H2 receptor antagonists(H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2 RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate(OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate(OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality(OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference(WMD),-0.70 unit; 95%CI:-1.64- 0.25] and the time that patients remained hospitalized [WMD,-0.77 d; 95%CI:-1.87- 0.34]. The Begg's test(P = 0.283) and Egger's test(P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2 RA, PPI may be a more effective therapy.

Head-to-head comparison of H_2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE).METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model.RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs,1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vsstandard dose H2RAs, 1.59 (95%CI, 1.44-1.75);standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis.CONCLUSION: H2RAS are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.

Spectrofluorimetric method for determination of some angiotensin II receptor antagonists

A simple, rapid, accurate and highly sensitive spectrofluorimetric method has been developed for determination of some angiotensin II receptor antagonists (AIIRA’s), namely Losartan potassium (Los-K), Irbesartan (Irb), Valsartan (Val) and Candesartan cilexetil (Cand) in pure forms as well as in their pharmaceutical dosage forms. All the variables affecting the relative fluorescence intensity (RFI) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefflcients (0.9982–0.9991) were obtained over the concentration range from 0.006 mg/mL to 1.7 mg/mL. Good accuracy and precision were successfully obtained for the analysis of tablets containing each drug alone or combined with hydrochlorothiazide (HCTZ) without interferences from the co-formulated HCTZ or the additives commonly present in tablets.

Medical therapy for clinical benign prostatic hyperplasia:α1 Antagonists,5α reductase inhibitors and their combination

Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting.

Hyperkalemia of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Hemodialysis: A Meta-analysis

The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated.Medline,Embase,the Cochrane Library,some databases of clinical trial registries,grey literatures,other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved.RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected.Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration’s RevMan 4.2 software package.The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs.control:RD=0.03,95% CI=-0.13?0.18,Z=0.34,P=0.73;ARBs vs.control:RD=-0.02,95% CI=-0.07?0.03,Z=0.75,P=0.45).However,there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs.control:WMD=0.10,95% CI=0.06?0.15,Z=4.64,P<0.00001;ARBs vs.control:WMD=-0.24,95% CI=-0.37--0.11,Z=3.58,P=0.0003).The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients,however the serum potassium could be increased with use of ACEIs in HD patients.Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation

BACKGROUND Cryoballoon ablation(CBA)is recommended for patients with paroxysmal atrial fibrillation(AF)refractory to antiarrhythmic drugs.However,only 80%of patients benefit from initial CBA.There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs)decreases the recurrence of AF postablation,particularly in nonparoxysmal AF undergoing radiofrequency ablation.The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown.We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia(AA)following CBA for paroxysmal AF.AIM To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF.METHODS We followed 103 patients(age 60.6±9.1 years,29%women)with paroxysmal AF undergoing CBA 1-year post procedure.Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring.A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence.RESULTS After a 1-year follow-up,19(18.4%)participants developed recurrence of AA.Use of ACEI or ARB therapy was noted in the study population.Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease.On a multivariate model adjusted for baseline demographics and risk factors for AF,ACEI or ARB therapy did not prevent recurrence of AA following CBA(P=0.72).Similarly,on Kaplan–Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA(P=0.2173).CONCLUSION In our study population,preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Angiotensin receptor blocker neprilysin inhibitors

Heart failure(HF)is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with,or eject,blood.It is a multifaceted clinical condition that affects up to 2%of the population in the developed world,and is linked to significant morbidity and mortality;it is therefore considered a major concern for public health.Regarding the mechanism of HF,three neurohumoral factors-the reninangiotensin-aldosterone system,the sympathetic nervous system,and natriuretic peptides—are related to the pathology of chronic HF(CHF),and the targets of treatment.Angiotensin receptor blocker and neprilysin inhibitor(angiotensinreceptor neprilysin inhibitor),namely sacubitril/valsartan(SAC/VAL),has been introduced as a treatment for CHF.SAC/VAL is an efficacious,safe,and costeffective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction(HFrEF),and reduces hospital admissions.An inhospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL.In the last five years,SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF.On the other hand,further work,with carefully designed and controlled preclinical studies,is necessary for understanding the molecular mechanisms,effects,and confirmation of issues such as long-term safety in both human and animal models.

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

Effects of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors on COVID-19

BACKGROUND The World Health Organization reported that 28637952 people worldwide had been infected with severe acute respiratory syndrome coronavirus 2,the causative agent of coronavirus disease 2019(COVID-19),by September 13.AIM The aim was to investigate whether long-term use of renin-angiotensin-aldosterone system(RAAS)inhibitors for the treatment of hypertension aggravates the performance of COVID-19 patients with hypertension.METHODS This was a retrospective analysis of lung computed tomography(CT)data and laboratory values of COVID-19 patients with hypertension who were admitted to Huoshenshan Hospital,Wuhan,Hubei Province,between February 18 and March 31,2020.Patients were divided into two groups.Group A included 19 people who were long-term users of RAAS inhibitors for hypertension;and group B included 28 people who were randomly selected from the database and matched with group A by age,sex,basic diseases,and long-term use of other antihypertensive drugs.All patients underwent a series of CT and laboratory tests.We compared the most severe CT images of the two groups and the laboratory examination results within 2 d of the corresponding CT images.RESULTS The time until the most severe CT images from the onset of COVID-19 was 30.37±14.25 d group A and 26.50±11.97 d in group B.The difference between the two groups was not significant(t=1.01,P=0.32).There were no significant differences in blood laboratory values,C-reactive protein,markers of cardiac injury,liver function,or kidney function between the two groups.There was no significant difference in the appearance of the CT images between the two groups.The semiquantitative scores of each involved lobe were 11.84±5.88 in group A and 10.36±6.04 group B.The difference was not significantly different(t=0.84,P=0.41).CONCLUSION Chest CT is an important imaging tool to monitor the characteristics of COVID-19 and the degree of lung injury.Chronic use of RAAS inhibitors is not related to the severity of COVID-19,and it does not worsen the clinical process.

Effect of valsartan on the expression of angiotensin II receptors in the lung of chronic antigen exposure rats

Background Many studies have suggested that angiotensin Ⅱ （Ang Ⅱ） and its receptors may be involved in the development of asthma. However, the expression of angiotensin Ⅱ receptors （AGTR） is not clear in the lung tissue of chronic asthmatics. This study was designed to determine the relationship between airway remodeling, dysfunction and the expression of AGTRs in a rat model of asthma. Methods Rats were sensitized with ovalbumin （OVA） for 2 weeks. Sixty minutes before an inhalation challenge, the rats were pretreated either with valsartan （15, 30, 50 mg.kg-1.d-1） or saline intragastrically. Then the rats received an OVA challenge for 30 alternative days. Acetylcholine （Ach）-induced bronchoconstriction was measured after the final antigen challenge. White cell counts in bronchoalveolar lavage fluid （BALF） and morphological changes in the airways were then assessed. The levels of transforming growth factor-beta 1 （TGF-β1） and platelet-derived growth factor （PDGF） in BALF were detected by ELISA. The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting. Results AGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls. The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness （mainly in small airways） in lungs of chronic antigen-exposed rats were positively correlated. Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats. However, AGTR2 mRNA and protein levels in the OVA-challenged rats and high-dose valsartan-treated rats （50 mg.kg-1.d-1） were also increased. Valsartan significantly decreased inflammatory cell accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats. Valsartan also decreased allergen-induced structural changes in rat airway （including total airway wall thickness and smooth muscle area） and the levels of TGF-β1 and PDGF in BALE Conclusions AGTR1 expression is potentially associated with airway remodeling and dysfunction in asthma. Ang Ⅱ and AGTR1 may participate in airway inflammation and airway remodeling of chronic antigen-exposed rats. Valsartan, a AGTR1 antagonist, could inhibit AGTR1 expression and partially inhibits structural airway changes as well as airway inflammation in chronic OVA-exposed rats.

Prevention of atrial fibrillation with renin-angiotensin system inhibitors on essential hypertensive patients:a meta-analysis of randomized controlled trials

We aimed to investigate the effectiveness and safety of angiotensin-converting enzyme inhibitors （ACEIs） or angiotensin Ⅱ receptor blockers （ARBs） on preventing atrial fibrillation in essential hypertensive patients. Systematic literature retrieval was carried out to obtain randomized controlled trials on the effects of ACEI/ ARBs on essential hypertensive patients before December, 2013. Data extraction and quality evaluation were performed. Meta-analysis was performed by Review Manager 5.2.3. Ten high quality studies （11 articles） with a total of 42,892 patients （20,491 patients in the ACEI/ARBs group and 22,401 patients in the β-blocker or the calcium antagonist group） met the inclusion criteria and were included in the meta-analysis. The results showed that ACEI/ARBs reduced the incidence of atrial fibrillation （AF） recurrence compared to calcium antagonists （RR=0.48; 95%CI, 0.40-0.58; P〈0.00001） or β-blockers （RR=0.39; 95%CI, 0.20-0.74; P=0.005） in long-term follow-up, respectively. Furthermore, ACEI/ARBs reduced the incidence of conges- tive heart failure （RR=0.86; 95%CI, 0.77-0.96; P=0.007）. However, no significant effects were observed on the incidence of new AF, cardiac death, myocardial infarction, and stroke. Our results suggest that ACEI/ ARBs may reduce the incidence of AF recurrence and congestive heart failure, with fewer serious adverse effects.

Effects of angiotensin-converting enzyme inhibitor and angiotensin Ⅱ receptor blocker on one-year outcomes of patients with atrial fibrillation: insights from a multicenter registry study in China

Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment.Baseline characteristics were carefully collected and analyzed.Logistic regression was utilized to identify the predictors of ACEI/ARB therapy.The primary endpoint was all-cause mortality,while the secondary endpoints included cardiovascular mortality,stroke and major adverse events(MAEs)during the one-year follow-up period.Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes.Results In total,759 AF patients(38.1%)were treated with ACEI/ARB.Compared with AF patients without ACEI/ARB therapy,patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF,hypertension,diabetes mellitus,heart failure(HF),left ventricular ejection fraction(LVEF)<40%,coronary artery disease(CAD),prior myocardial infarction(MI),left ventricular hypertrophy,tobacco use and concomitant medications(all P<0.05).Hypertension,HF,LVEF<40%,CAD,prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment.Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality[hazard ratio(HR)(95%CI):0.682(0.527-0.882),P=0.003],cardiovascular mortality[HR(95%CI):0.713(0.514-0.988),P=0.042]and MAEs[HR(95%CI):0.698(0.568-0.859),P=0.001].The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis.Conclusions In patients with AF,ACEI/ARB was related to significantly reduced one-year all-cause mortality,cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.

Effects of angiotensin Ⅱ receptor antagonist, Losartan on the apoptosis, proliferation and migration of the human pancreatic stellate cells

AIM: To investigate the effects of AT1 (Type 1 angiotensin Ⅱ receptor) antagonist (Losartan) on the apoptosis,proliferation and migration of the human pancreaticstellate cells (hPSCs).METHODS: hPSCs were isolated from pancreatic sample of patients with pancreatic carcinoma using radioimmunoassay (RIA) technique to detect the concentration of AngⅡ in culture media and cell homogenate. Immunocytochemistry (ICC) and in situ hybridization (ISH) methods were utilized to test AT1 expression in hPSCs. Effects of Losartan on hPSCs proliferation, apoptosis and migration were investigated using BrdU incorporation, TUNEL, flow cytometry (FCM),and phase-contrast microscope separately when cells treated with Losartan. Immunofluorescence and Western blot were applied to quantify the expression of type Ⅰ collagen in hPSCs.RESULTS: There exists AT1 expression in hPSCs, while no AngⅡ was detected in culture media and cell homogenate. Losartan induces cell apoptosis in a doseand time-dependent manner (apparently at 10-5 mol/L),no pro-proliferative effect was observed in the same condition.Corresponding dosage of Losartan can also alleviate the motion capability and type Ⅰ collagen content of hPSCs compared with AngⅡ treatment and non-treatment control groups.CONCLUSION: These findings suggest that paracrine not autocrine functions of AngⅡ may have effects on hPSCs,which was mediated by AT1 expressed on cells, while Losartan may exert anti-fibrotic effects by inhibiting hPSCs motion and partly by inducing apoptosis.

Stronger inhibition of gastric acid secretion by lafutidine, a novel H_2 receptor antagonist, than by the proton pump inhibitor lansoprazole

AIM: To compare the antisecretory activity and plasma drug concentrations of a single oral dose of 10 mg lafutidine, a novel H2 receptor antagonist, with those of the proton pump inhibitor lansoprazole (LPZ) 30 mg. METHODS: Ten volunteers without H pylori infection participated in this crossover study comparing lafutidine 10 mg with LPZ 30 mg. Intragastric pH was monitored for 6 h in all participants, and blood samples were collected from four randomly selected individuals after single-dose administration of each drug. RESULTS: The median intragastric pH was significantly higher in individuals who received lafutidine 10 mg than in those who received LPZ 30 mg 2, 3, 4, 5, and 6 h after administration. Maximal plasma drug concentration was reached more promptly with lafutidine 10 mg than with LPZ 30 mg. CONCLUSION: In H pylori-negative individuals, gastric acid secretion is more markedly inhibited by lafutidinethan by LPZ.

Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy

The use of renin-angiotensin system(RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-Ⅱreceptor blockers, to slow progression of chronic kidney disease(CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults,among them a lack of focus on the elderly. However,it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression ofkidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patientcentric goal of therapy for many elderly individuals should be individualized.

Assessment of Effect of Angiotensin Ⅱ Receptor Antagonist Losartan on Aortic Distensibility in Patients With Essential Hypertension by Echocardiography

Summary: The effects of angiotensin Ⅱ receptor antagonist losartan on elastic properties of aorta in patients with mild to moderate essential hypertension were assessed. The ascending aortic distensibility in 26 patients (48±3 years) with mild to moderate essential hypertension before and after 12 weeks of treatment with losartan (50 mg/day) was evaluated by using two-dimensional echocardiography. M-mode measurements of aortic systolic (D s) and diastolic diameter (D d) were taken at a level approximately 3 cm above the aortic valve. Simultaneously, cuff brachial artery systolic (SBP) and diastolic(DBP) pressures were measured. Aortic pressure-strain elastic modulus (E p) was calculated as D d×(SBP-DBP)/(D s-D d)×1333 and stiffness index beta (β) was defined as D d×Ln (SBP/DBP)/(D s-D d). Blood pressure significantly decreased from 148±13/95±9 mmHg to 138±12/88±8 mmHg (systolic blood pressure, P=0.001; diastolic blood pressure, P=0.003). There was no significant difference in pulse pressure before and after treatment with losartan (53±10 mmHg vs 50±7 mmHg). The distensibility of ascending aorta increased significantly as showed by the significant decrease in pressure-strain elastic modulus from 4.42±5.79×10 6 dynes/cm 2 to 1.99±1.49×10 6 dynes/cm 2 (P=0.02) and stiffness index beta from 27.4±32.9 to 13.3±9.9 (P=0.02). Although there was a weak correlation between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in diastolic blood pressure after losartan treatment(r=0.40, P=0.04 and r=0.55, P=0.004, respectively), no correlation was found between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in systolic blood pressure (r=0.04, P=0.8 and r=0.24, P=0.2, respectively). Our study demonstrated that angiotensin Ⅱ receptor antagonist losartan has a beneficial effect on aortic distensibility in patients with mild to moderate essential hypertension and this effect is partly independent of blood pressure reduction.

Evaluation of a novel angiotensin II receptor 1 antagonist intesartan as anti-hypertension drug

Aim The preclinical studies of a novel angiotensin II receptor 1 antagonist 2-（4-（ （1,7＇-dimethyl-2＇- propyl-1H ,3 ＇H-2,5＇-bibenzo [ d ] imidazol-3＇-yl ） methyl） -1H-indol-l-yl ） benzoic acid （ intesartan ）. Methods The affinity to AT1 receptor of intesartan was tested through radioactive receptor binding assay by -y-counter. The anti-hypertensive activity in spontaneously hypertensive rats （SHRs） at different doses in vivo was tested by tail noninvasive arterial blood pressure measurement system. Pharmacokinetic parameters were analyzed by high per- formance liquid chromatography （HPLC） method. Besides, acute toxicity tests in ICR and Ames reverse mutation assay in tester strain （TA97, TA98, TA100 and TA102） was also detected. Results The binding assays sugges- ted that intesartan displayed high affinity to angiotensin II AT1 receptor with an ICs0 value of （0.36 ± 0. 18） nmol · L^-1. In vivo anti-hypertensive experiments showed that intesartan had an efficient and long-acting effect in reduc- ing blood pressure which could last more than 24 h at the doses of 2 mg· kg^-1, 5 mg · kg^-1 , and 10 mg · kg^-1 in spontaneously hypertensive rats. The minimum effective dose of it was 2 mg · kg^-1 and the T/P value was 54. 18%. Acute toxicity tests suggested that intesartan was safe with the LDs0 value of 526.20 mg · kg^-1. Ames assay proved that it would not cause the mutations of salmonella typhimurium. And the pharmacokinetic experiments showed that it could be absorbed efficiently and metabolized smoothly both in blood and in tissues in wistar rats. Conclusions Intesartan could be considered as a novel anti-hypertension candidate with efficient, long-acting and low toxicity chracteristics.