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Objective To evaluate the effects of renin-angiotensin system (RAS) blockades [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin Ⅱ type 1 receptor blockers (ARB)]on contrast-induced nephropathy (CIN) in patients undergoing angiography.Methods Pubmed,Embase,Cochrane library,Wanfang database and CNKI were searched.The literature limited range was from their start year to July 2015.Randomized controlled trials (RCTs) and non-randomized controlled trials of renin-angiotensin system blockades in influencing CIN were assessed.Two investigators extracted data and performed quality analysis independently from all trims included.Rev man 5.3 software was used.Results 16 trials with a total of 15 897 patients were identified.There were 7490 patients who received renin-angiotensin system blockades and 8407 patients in control group.The meta analysis revealed a higher CIN incidence in ACEI/ARB group than that in control group (14.35％ vs 12.13％,P=0.04,OR=1.44,95％CI 1.01-2.04).For patients with renal insufficiency,ACEI/ARB group had a higher CIN incidence than control group (12.23％ vs 7.32％,P=0.02,OR=1.80,95％CI 1.10-2.94),and the serum creatinine changes in ACEI/ARB group were higher than those in control group.There was statistical difference in serum creatinine changes between groups (P=0.02,MD=0.08,95％CI 0.02-0.15).Conclusions Renin-angiotensin system blockades can increase theincidence of CIN in patients undergoing angiography.Renin-angiotensin system blockades can contribute to CIN for patients with renal insufficiency.
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Objective To compare effects of irbesartan and captopril on left ventricular function in elderly patients with cardiovascular disease and cardiac functional reserve .Methods 100 cases of elderly patients with car-diovascular disease were chosen ,according to a list of numbers randomly divided into the two groups ,50 cases in each group,a group with irbesartan treatment ,as the irbesartan group and the other group received captopril ,as the capto-pril group compared the two groups of patients left ventricular function and cardiac functional reserve .Results (1) Left ventricular function after the irbesartan group therapy LVDd indicators ,IVSd,LVPWd,LVEF,VE/VA,LVM was significantly better than before treatment ,the difference was statistically significant (t=31.23,18.36,28.12,46.36, 51.13,16.03,all P<0.05),the captopril group before and after treatment was significantly better than the treatment of various indicators,the difference was statistically significant (t=24.53,21.36,31.12,14.33,18.19,16.45,all P<0.05);(2) The irbesartan group of patients after treatment resting heart rate ,exercise heart rate,6min walking distance improved significantly over the treatment of former CCRI and CRI ,the difference was statistically significant (t=39.09,23.77,39.01,23.18,22.45,all P<0.05),after treatment with captopril treatment was significantly better than the indexes,the difference was statistically significant (t=91.21,37.16,26.74,46.33,36.74,all P<0.05),6min walking distance from the irbesartan group therapy ,CRI better than the captopril group ,the difference was statistically significant(t=39.02,42.14,all P<0.05).Conclusion Irbesartan and captopril on improving left ventricular function in elderly patients with cardiovascular disease and cardiac reserve function has a significant effect,irbesartan 6min walking distance test and cardiac reserve indices better .
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Angiotensin (Ang Ⅱ),a main effector peptide of the renin-angiotensin system (RAS),mediates a hormonal action in the maintenance of blood pressure and electrolyte levels,and thus fluid homeostasis.Recent studies have implicated that it correlates with tumor growth,angiogenesis,metastasis and it has drawn more and more attention.Many studies show that Ang Ⅱ-AT1R/AT2R play crucial roles in tumor growth,metastasis,invasion and tumor angiogenesis,which are formed new targets for treating malignant tumors.
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Objective To explore the relationship between renin-angiotensin system (RAS) blockers and plasma lev-el of adiponectin (APN) in patients with metabolic syndrome (Mets). Methods Fifty-three patients with Mets were random-ized into control group (n=23), angiotensin-convertingenzyme inhibitor (ACEI) group (benidipine, 5 mg/d, n=15) and angio-tensinll recepter blockers(ARB)group (candesartan, 4 mg/d, n=15),and were given 4-week treatment. Twenty-three pa-tients, who were avoiding application related drugs affecting the RAS for four weeks, were used as control. The values of plas-ma APN, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), creatinine(CR), aspartate aminotransferase (ALT), bil-irubin (BIL) and insulin resistance index (HOMA-IR) were detected and compared before and after treatment. Results The levels of FBG and LDL-C were significantly decreased after treatment than those before treatment in ACEI group. The level of CR was significantly lower after treatment than that before treatment in ARB group (P＜0.05). The plasma APN level was significantly higher after treatment compared to that before treatment in ACEI and ARB groups (P＜0.01).There were no sig-nificant differences in the values of FINS,HOMA-IR,TC,ALT and BIL between 'before and after treatment' in three groups (P>0.05). The levels of CR, TC, ALT and BIL before treatment were influencing factors for the APN level. The levels of FBG and TC after treatment were influencing factors for the APN level. Conclusion APN may serve as potential therapeu-tic targets for treating Mets and its related complications by ACEI and ARB.
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Objective To investigate the effect of angiotensin Ⅱ (Ang Ⅱ) type 1 receptor blocker (ARB) on 12-lipoxygenase (12-LO) activity and P-cadherin expression in type 2 diabetic rat glomeruli.Methods Podocytes were stimulated by 107 mol/L Ang Ⅱ for 24 hours.12(S)-HETE (1mg· kg 1 · d-1) and Ang Ⅱ (400 ng· kg-1· min-1) were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed with high fat diet received low dose streptozotocin (STZ) to make type 2 diabetes and divided into 2 groups:low dose STZ (DN group),low dose STZ + ARB treatment (Losartan group).Rats fed with regular chow were used as control group.All the rats were sacrificed after 6 weeks.Urine,blood,kidney cortical tissue and isolated glomeruli by sieving method were collected at the end of study respectively.ELISA,RT-PCR and Western blotting for related target were performed respectively.Results Ang Ⅱ increased 12(S)-HETE levels in podocytes and glomeruli (all P ＜ 0.01).Ang Ⅱ levels in the glomeruli were significantly increased by 12(S)-HETE stimulation (P ＜0.01).Blood glucose,kidney/body weight and 24 hour urinary protein were increased in DN group compared with that in control group (all P ＜ 0.01).However,urine protein,Kidney/body weight were decreased in Losartan group compared with DN group (all P ＜ 0.05).Increment of 12(S)-HETE content and decrement of P-cadherin expression were observed in DN glomeruli compared with that in control group(all P ＜ 0.01).These abnormalities were prevented by administration of the losartan (all P ＜ 0.05).Conclusions Ang Ⅱ can down-regulate glomerular P-cadherin expression via activation of 12-LO.ARB can ameliorate the progression of DN via up-regulation of glomerular P-cadherin through inhibition of 12-LO activation in type 2 DN rats.
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Objective To identify susceptible miRNAs for the pathogenesis of diabetic nephropathy (DN) and the molecular targets of losartan treatment. Methods The 8-week age KKAy mice were divided into losartan treatment group (10 mg· kg-1· d-1) and non-treatment group,C57BL/6 mice were used as the control group.At age of 20 weeks,body weight,random blood glucose,urinary albumin and urinary creatinine were tested,and kidney morphology was observed.Glomeroli were separated by magnetic beads perfusion,and total RNA were extracted.MiRNAs expression profiles were analyzed by the Affymetrix GeneChip miRNAs arrays. Results At age of 20 weeks,KKAy mice developed higher body weight,higher blood glucose and higher urinary microalbumin creatinine ratio than C57BL/6 mice,and the glomerular basement membrane thickened,mesangial matrix widened.Losartan treatment markedly improved the level of urinary albumin creatinine ratio [(539.71±100.23) mg/g vs (728±177.19) mg/g,P＜0.05)] and pathological lesion of KKAy mice.The miRNA array analysis showed that there were 22 miRNAs differentially expressed between KKAy non-treatment mice and C57BL/6 mice glomeruli at age of 20 weeks.Among them,10 miRNAs were up-regulated,and 12 miRNAs were down-regulated.The expression of 4 miRNAs was down-regulated in glumeruli of KKAy mice treated by losartan compared with that of non-treatment mice.The expressions of miRNA-503 and miRNA-181d were significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment, Conclusion The expressions of miRNA-503 and miRNA-181d are significantly up-regulated in the glumeruli of KKAy mice and inhibited by losartan treatment,which may be new therapeutic targets of DN.
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Blood pressure remains the single most important modifiable risk factor for the primary and secondary prevention of stroke. The landmark trial of the Perindoprii Protection Against Recurrent Stroke Study (PROGRESS) has suggested that the antihypertensive treatment with angiotensin-converting enzyme inhibitor (ACEI) perindopril at least 2 weeks after stroke may reduce the risks of recurrent stroke and other cardiovascular events. Although most systematic reviews have suggested that the efficacy of almost all types of antihypertensive drugs is similar in the prevention of stroke,there are also some important exceptions. The Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) has demonstrated that the angiotensin receptor blockers (ARB) telmisartan was equivalent to ramipril for preventing cardiovascular events in patients with vascular disease or diabetes; while in a similar population,ramipril was quite effective for preventing stroke. It is speculated according to the moderating effects of ARB on the renin-angiotensin-aldosterone system that its protective effects against stroke is superior to other antihypertensives. However,many clinical trials have suggested that ARB does not have unique role in stroke prevention. Therefore,whether ARB should be regarded as the first-line drags for stroke prevention in both primary and secondary prevention settings has been controversial.
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Objective To investigate the mechanism of the effects of heavy alcohol consumption in a short term and the protection of angiotensin Ⅱ receptor blocker (valsartan) on cardiac function in rats. Methods The 42 male Wistar rats aged 20 weeks were randomly divided into 4 groups:control group (group C, n= 10), alcohol group (group A, n=10), low-dose valsartan group (LD group, n= 11) and high-dose valsartan group (HD group, n= 11). They were supplied with same animal feeds, but all of them were administered different dose of alcohol and medicine via intragastric tube: group C was administered water, group A was administered alcohol (6. 4 g/kg), LD group was administered alcohol (6.4 g/kg) and valsartan (15 mg/kg), HD group was administered alcohol (6.4 g/kg) and valsartan (30 mg/kg). And 9 weeks later, the change of cardiac function was observed by echocardiography, the body and heart weight were measured, the hydroxyproline content of rat myocardium was determined by sample alkaline solution. Results After 9 weeks, there were no significant differences among four groups in left ventricular ejection fraction (LVEF), stroke volume (SV) and fraction shortening (FS). But the E peak, Ea/Aa, Ea peak and Aa peak were obviously lower in group A than in groups of C, LD and HD (all P＜0.05), and there were significant differences among C group, LD group and HD group in E peak, Ea/Aa (all P＜0. 05). The HW/BW and hydroxproline (Hyp) contents of myocardium were higher in group A than in groups of C, LD and HD (all P＜0. 01), but there were no statistical significances among group C, LD group and HD group (all P＞0. 05). Conclusions The short term heavy alcohol consumption results in impaired ultrastructure and diastolic function of myocardium in rats, the angiotensin Ⅱ receptor blocker (valsartan) may protect it.
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Objective To observe the curative effect of telmisartan on sinus rhythm maintenance in patients with nonvalvular paroxysmal atrial fibrillation (AF) after the recovery of sinus rhythm with amiodarone. Methods Seventy-six patients with nonvalvular paroxysmal atrial fibrillation who visited our hospital were randomly divided into two groups: control group (amiodarone, n=36) and treatment group (telmisartan plus amiodarone, n=40). The maintenance of sinus rhythm and the change of left atrial diameter between the two groups at 3, 6 and 12 months after therapy were observed. Results The left atrial diameter and the maintenance rate of sinus rhythm between the two groups at 3 and 6 months after therapy had no statistically significant difference (t=0.04, 0.51, 0.03, 1.12, all P>0.05). After 1-year treatment, the maintenance rates of sinus rhythm were 48.4% and 73.5% in treatment group and control group ,respectively (t=4.33,P<0.05), and the left atrial diameter was significantly shorter in treatment group than in control group [(34.38±3.85) mm vs. (37.26±4.85)mm ,t=2.66, P<0.05]. Conclusions The combination of telmisartan and amiodarone is more effective than amiodarone alone on maintenance of sinus rhythm in patients with nonvalvular paroxysmal AF after the recovery of AF. The curative effect may be due to telmisartan effects on inhibiting the activation of renin-angiotensin system, decreaseing the cardiac burden and delaying the cardiac remodeling.
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Objective To observe the effects and the functions of valsartan and simvastatin in early diabetic nephropathy. Methods A total of 80 patients with early diabetic nephropahy were randomly divided into two groups.The patients in control group(n=40)received valsartan at a dose of 80rag/day ,while in treated group(n=40)on the base of the same treatment as control group, added simvastatin 20 mg/everyrfight. To compare the differences of lipids,urine albumin excretion rate(UAER) and C-reactive protein(CRP) before or after treatments through 12 weeks. Re-sults The UAER of two groups decreased obviously after therapy,especially the treated group(P<0.01) ;the lipids and CRP also decreased evidently in the treated group (P<0.05). Conclusion The lipids, UAER, CRP of patients in early diabetic nephropathy could be down-regulated,with combined medication of the simvastatin and valsartan, and the injury of renal alleviated.
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Angiotensin-Ⅱ-induced apoptosis was widely involved in the pathogenesis of diabetes mellitus, cardiovascular diseases, etc. The mechanism of angiotensin-Ⅱ-induced apoptosis is complicated, including the receptor (AT1R and AT2R) level regulation, Fas/FasL pathway, and the regulation by p53 family, Bcl-2 family, Caspase family, Ang-(1-7), etc. Mitochondria damage and oxidative damage play important roles in the apoptosis process. This article reviews the previous researches on angiotensin-Ⅱ-induced apoptosis.
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Objective To investigate whether and how candesartan treatment can attenuate the deleterious influence of hyperglycemia in diabetic(db/db) mice.Methods Eight-week-old db/db mice were randomized into candesartan eilexetil (1 mg/kg) or placebo group via gavage for 6 weeks.Their age-matched nondiabetie littermates db/m mice were treated with placebo and acted as non-diabetic control group.After 6 weeks' treatment, intraperitoneal glucose tolerance test,immunohistochemical stainings of oxidative stress markers [8-(OH) dG,4- HNE,NADPH oxidase],insulin,CD31,Azan staining and electron microscopy observation of islet?-cells were perfermed.Results As compared with placebo group,the improvement in glucose tolerance and marked saving of islet?-cell mass with candesartan for 6 weeks were noted.There were also notably decreased staining intensity in oxidative stress markers,such as 8-(OH) dG,4-HNE,p22~(phox),gp91~(phox),as well as attenuated intra-islet Azan staining and enhanced endothelium marker CD31 staining in islet.Under electron microscope,candesartan-treated mice showed significantly increased granulation of insulin and ameliorated proliferations of endoplasmic reticulum and Golgi bodies.Furthermore,swelling of mitochondria was relieved to nearly normal.Conclusion After diabetic onset,candesartan treatment does not reverse the state of diabetes but may effectively improve glucose tolerance and protect?-cell function by attenuating oxidative stress,islet fibrosis,sparsity of blood supply and uhrastructure disruption,and thus delays the?-cell failure.