Changes of serum vascular endothelial growth factor, apelin and heme oxygenase-1 levels in patients with type 2 diabetes mellitus and their relationship with diabetic retinopathy / 中华眼底病杂志

Objective To observe the serum vascular endothelial growth factor (VEGF),apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR).Methods A total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study.Vision,slit lamp microscope,indirect ophthalmoscope and FFA examinations were performed on all the subjects.According to the results of the examinations combined with the DR clinical staging criteria,the patients were divided into non-DR (NDR) group,non-proliferative DR (NPDR) group,and proliferative DR (PDR) group,with 72,76 and 60 patients in each,respectively.The clinical data of each group were recorded,and the levels of fasting blood glucose (FPG),HbA1c,total cholesterol (TC),three acylglycerol (TG),high density lipoprotein (HDL-C),low density lipoprotein (LDL-C),VEGF,apelin and HO-1 were detected in each group.The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF,apelin and HO-1 in predicting the occurrence of PDR.Correlation analysis of serum VEGF,Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis.Results The level of VEGF (56.82± 10.16 vs 91.74±22.83,140.15±36.40,195.28±42.26 pg/ml)and apelin (2.95±0.53 vs 4.68±0.74,7.25±1.13,10.16± 1.35 ng/ml) in PDR group were significantly higher than those in NPDR,NDR and control groups (F=17.306,21.814;P＜0.05).The level of HO-1 (50.37±10.14 vs 43.58±8.16,30.25t6.28,22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR,NDR and control groups (F=15.827,P＜0.05).The ROC curve analysis showed that the best cut-offvalues of serum VEGF,apelin and HO-1 were 162.50 pg/ml,8.30 ng/ml,27.13 mmol/L,and the three combined to predict PDR of AUC (95％CI)was 0.906 (0.849-0.962),and their sensitivity (90.3％) and specificity (83％) were better.The correlation analysis showed that the VEGF,apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382,0.416,-0.36;P＜0.05),FPG (r=0.438,0.460,-0.397;P＜0.05) and HbAlc (r=0.375,0.478,-0.405;P＜0.05),and the serum VEGF were correlated with apelin and HO-1 (r=0.793,-0.594;P＜0.01).Conclusion Elevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR,and the three combination helps predict the occurrence of PDR.

Role of angiotensin Ⅱ type 2 receptor in repeated propofol anesthesia-induced neuroapoptosis in basal ganglia of newborn rats / 中华麻醉学杂志

Objective To evaluate the role of the angiotensin Ⅱ type 2 receptor (AT2R) in repeated propofol anesthesia-induced neuroapoptosis in the basal ganglia of newborn rats.Methods Fiftyfour pathogen-free Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),repeated propofol anesthesia group (group P) and AT2R agonist CGP42112A group (group G).In group C,0.9％ sodium chloride injection 3 ml/kg was intraperitoneally injected,and half of the initial dose 1.5 ml/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group P,propofol 30 mg/kg was intraperitoneally injected,and half of the initial dose 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group G,CGP42112A 1 mg/kg was intraperitoneally injected,propofol 30 mg/kg was intraperitoneally injected 5 min later,and half of the initial dose of propofol 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.Six rats were sacrificed at 2 h after emergence from anesthesia,and brains were removed for detection of neuroapoptosis in the basal ganglia by TUNEL assay.The apoptosis index was calculated.Another 6 rats were sacrificed,and the basal ganglia were isolated from brains to detect the expression of activated caspase-3,AT2R and peroxisome proliferator-activated receptor gamma (PPARγ) (by Western blot) and the expression of AT2R and PPARγ mRNA (by real-time polymerase chain reaction).The other 6 rats were fed until 28 days old,and the cognitive function was then assessed using Morris water maze test.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the target quadrant was shortened,the frequency of crossing the platform was decreased,the apoptosis index of the basal ganglia was increased,the expression of activated caspase-3 was up-regulated,and the expression of AT2R and PPARγprotein and mRNA was down-regulated in group P (P＜0.05),and no significant change was found in the parameters mentioned above in group G (P＞0.05).Compared with group P,the escape latency was significantly shortened,the time of staying at the target quadrant was prolonged,the frequency of crossing the platform was increased,the apoptosis index of the basal ganglia was decreased,the expression of activated caspase-3 was down-regulated,and the expression of AT2R and PPARγ protein and mRNA was up-regulated in group G (P＜0.05).Conclusion Inhibited activation of AT2R is involved in repeated propofol anesthesia-induced neuroapoptosis in the basal ganglia of newborn rats.

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension

The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1–7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1–7)/Mas receptor and ACE2/Ang-(1–9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

Role of angiotensin H type 2 receptor in repeated propofol anesthesia-induced neuroapoptosis in hippocampus of newborn rats / 中华麻醉学杂志

Objective To evaluate the role of the angiotensin Ⅱ type 2 receptor (AT2R) in repeated propofol anesthesia-induced neuroapoptosis in the hippocampus of newborn rats.Methods Fiftyfour pathogen-free Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),repeated propofol anesthesia group (group P) and AT2R agouist CGP42112A group (group G).In group C,0.9％ sodium chloride injection 3 ml/kg was intraperitoneally injected,and half of the initial dose 1.5 ml/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group P,propofol 30 mg/kg was intraperitoneally injected,and half of the initial dose 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group G,a single bolus of CGP42112A 1 mg/kg was intraperitoneally injected,propofol 30 mg/kg was intraperitoneally injected 5 min later,and half of the initial dose of propofol 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.At 2 h after emergence from anesthesia,6 rats were sacrificed and brains were removed for detection of neuroapoptosis in the hippocampus by TUNEL assay.The apoptosis index was calculated.Another 6 rats were sacrificed,brains were removed and hippocampi were isolated for determination of the expression of activated caspase-3,AT2R and peroxisome proliferator-activated receptor gamma (PPARγ) in hippocampal tissues by Western blot.The other 6 rats were fed until 28 days old,and the cognitive function was then assessed using Morris water maze test.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the target quadrant was shortened,the frequency of crossing the platform was decreased,the apoptosis index was increased,the expression of activated caspase-3 was up-regulated,and the expression of AT2R and PPARγ was down-regulated in group P (P＜0.05),and no significant change was found in the parameters mentioned above in group G (P＞0.05).Compared with group P,the escape latency was significantly shortened.the time of staying at the target quadrant was prolonged,the frequency of crossing the platform was increased,the apoptosis index was decreased,the expression of activated caspase-3 was down-regulated,and the expression of AT2R and PPARγ was up-regulated in group G (P＜0.05).Conclusion Inhibited activity of AT2R is involved in repeated propofol anesthesia-induced neuroapoptosis in the hippocampus of newborn rats.

Regulation of AT1-calcineurin Signaling Pathway on Transient Outward Potassium Ion Channel Remolding in Hypertrophic Atrial Myocytes of Neonatal Rats / 中国循环杂志

Objective: To explore the role of angiotensin receptor type I (AT1)-calcineurin (CaN) signaling pathway in transient outward potassium ion channel (Ito) remolding in hypertrophic atrial myocytes of neonatal rats. Methods: 1 day old neonatal rats’ atrial myocytes were isolated and the cells were divided into 4 groups:①Control group, normal cells were cultured for 24 h,②Stretching group, the cells were cultured for 24 h with mechanical stretching to induce hypertrophy,③Telmisartan group, the cells were treated by telmisartan at 1 μmol/L for 1 h, then cultured for 24 h and ④Cyclosporin-A (CsA) group, the cells were treated by CsA at 0.25 μg/ml for 1 h, then cultured for 24 h. The ratios of protein/DNA in myocytes were compared between Control group and Stretching group, cell hypertrophy was deifned by mRNA expression of atrial natriuretic peptide (ANP). Ito changes were detected by whole-cell patch clamping technique, proteins expressions of Kv4.3 and CaN A subunit were examined by Western blot analysis. Results: Compared with Control group, Stretching group showed obviously decreased Ito density and Kv4.3 protein expression, while increased CaN A protein expression; Compared with Stretching group, the above effects were reduced in Telmisartan group and CsA group. Conclusion: AT1-CaN signaling pathway was involved in the regulation of Ito channel remodeling in hypertrophic atrial myocytes of neonatal rats.

Changes of Gene Expressions in Spontaneously Hypertensive Rat Model After Losartan Treatment

BACKGROUND AND OBJECTIVES: The renin angiotensin system seems to play an important role in the development of cardiac and vascular hypertrophy in hypertension. The changes in pathology, and gene expressions of the angiotensin II receptor type 1A (ATIA) and angiotensin converting enzyme (ACE) were investigated in order to explore the effects of losartan in spontaneously hypertensive rat (SHR) models. MATERIALS AND METHODS: Twelve week-old male Wistar rats were grouped as follows: control (C) group, hypertension (H) group, and losartan (L) group in which SHR was treated with losartan (10 mg/kg/day). Western blot and reverse transcription-polymerase chain reaction analysis regarding seven genes such as endothelin-1, ACE, ATIA, neutrophil cytosolic factor, brain natriuretic peptide, troponin I, endothelial nitric oxide synthase were performed. RESULTS: Systolic blood pressure was significantly decreased in the L group compared with the H group in weeks 3 and 5. ACE and ATIA proteins in the L group were lower than H group in week 5. CONCLUSION: Losartan reduced blood pressure, cardiac hypertrophy and protein expressions of ACE and ATIA. Changes of protein expressions were more sensitive than changes in pathology. Further study is needed for the differing doses of losartan in SHR models.

Should angiotensin receptor blockers be regarded as first-line drugs for stroke prevention in both primary and secondary prevention settings? / 国际脑血管病杂志

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.

PPARgamma Agonist and Angiotensin II Receptor Antagonist Ameliorate Renal Tubulointerstitial Fibrosis

The peroxisome proliferator activated receptor (PPAR)gamma agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARgamma agonist and interaction with angiotensin receptor antagonist in the unilateral ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT), pioglitazone treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14, CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis. The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of TGF-beta1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the pioglitazone inhibited tubulointerstitial fibrosis, however, the synergism between pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1 and TGF-beta/Smad2 in the treated groups, PAI-1 and TGF-beta are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARgamma agonist might be used in the treatment of renal fibrotic disease.

The effect of Valsartan and Captopril for the improvement of left ventricular systolic function after acute anterior myocardial infarction / 中华核医学杂志

Objective To compare the therapeutic effect of angiotensin Ⅱ antagonist (Valsartan)and angiotension-converting enzyme inhibitor (Captopril) for the improvement of left ventricular systolic function(LVSF) after acute myocardial infarction (AMI) at anterior wall. Methods A total of 75 patients with initial AMI at anterior wall were enlisted in the study. Patients were divided randomly into three groups: control group (n = 15), Captopril treated (n =30), and Valsartan treated (n =30). At 1 week and 28 weeks post AMI, the LVSF and left ventricular regional ejection fraction (LrEF) were measured by equilibrium radionuclide angiography (ERNA). The t-test was used to compare the dada. Results ( 1 ) At 28 weeks, left ventricular ejection fraction (LVEF) and left ventricular peak ejection rate (LPER) in Valsartan treated group were significantly increased as compared with those of control: ( 59.4 ± 8.6 ) % vs (44.9 ± 8.4)%, t = 3.87, P ＜ 0.01 for LVEF; (3.89 ± 1.01 ) end-diastolic volume (EDV)/s vs (2.84 ±1.05) EDV/s, t= 4.16, P ＜ 0.01 for LPER). The left ventricular time to peak ejection rate (LTPER) in Valsartan treated group was significantly decreased ( ( 116 ± 16 )ms vs ( 137 ±20) ms, t =2.16, P ＜ 0.05 ) as compared with control. (2)Compared with 1-week, 28-week Valsartan treated group had a significant increase inLrEF2, LrEF4, LrEF5, LrEF6: (71.6±18.8)% vs (57.0±11.4)%, t=2.11, P＜0.05;(78.1 ±16.8)% vs (68.9±21.0)%, t =2.06, P＜0.05; (70.5±16.9)% vs (59.9 ±23.4)%, t=1.99, P ＜ 0.05; and (58.1 ± 9.0) % vs (46.0 ± 18.9) %, t = 2.43, P ＜ 0.05, respectively. Conclusions Valsartan and Captopril are effective for the improvement of LVEF after AMI at anterior wall. The effects of the two drugs are similar.

Renal protection of rosiglitazone in hypertensive rats and its relationship with the expression of angiotensin Ⅱ receptors / 中华肾脏病杂志

Objective To observe the role of rosiglitazone in unclipped kidneys of two-kidney- one-clip hypertensive rats and examine its relationship to angiotensinⅡreceptors.Methods Two- kidney-one-clip hypertensive rats were divided randomly into 4 groups as follows:positive control group (CONT),traditional antihypertensive drugs group (TAHD,reserpine 50?g?kg~(-1)?d~(-1), dihydralazine 6.25 mg?kg~(-1)?d~(-1) and hydrochlorothiazide 6.25 mg?kg~(-1)?d~(-1),regular-dose rosiglitazone group (RRGL,rosiglitazone 5 mg?kg~(-1)?d~(-1)),and high-dose rosiglitazone group (HRGL, rosiglitazone 20 mg?kg~(-1)?d~(-1)).Sham operation rats were as negative controls.Each group had 8 rats. Animals were monitored and sacrificed at 10th week.Results Blood systolic pressure in TAHD group and HRGL group was significantly lower than that in CONT group [TAHD(137?27 ) mm Hg and HRGL (143?16) mm Hg vs CONT (191?25 ) mm Hg,P＜0.05],but no significant difference between the former two groups was found.Nor did the blood systolic pressure between RRGL group [(176?18) mm Hg] and CONT group.At 10th week,rats in SHAM group and treated groups had lower urinary urinary protein excretion rate,glomerular injury score and wall-to-lumen ratio of arteriole than those in CONT group [vs CONT urinary protein excretion rate (44.60?17.40) mg/24 h,P＜0.05; vs CONT glomerular injury score 60.85?33.05,P＜0.05;vs CONT wall-to-lumen ratio of arteriole 2.33?1.01,P＜0.01,except TAHD group].Though with the similar level of blood pressure,blood glucose and lipid,HRGL,compared with TAHD group showed lower urinary protein excretion rate [HRGL (16.78?3.50) mg/24 h vs TAHD (27.94?12.79) mg/24 h,P＜0.05],decreased glomerular injury score (HRGL 18.04?7.76 vs TAHD 27.92?6.39,P＜0.05) and wall-to-lumen ratio of arteriole (HRGL 1.75?0.38 vs TAHD 2.16?0.90,P＜0.05) in the cortexes of unclipped right kidneys.The expression of type 1 angiotensinⅡreceptor (AT1R) mRNA was no difference in HRGL group and TAHD group,but the expression of type 2 angiotensinⅡreceptor (AT2R) mRNA was more intensive in HRGL group.Conclusion Rosiglitazone can protect the kidneys from hypertensive injury,especially in high dose.The beneficial effects seem incompletely dependent on the metabolism modulating and reduction of blood pressure,but in relationship to the upregulation of AT2R mRNA.

Expression of angiotensin Ⅱ type 1 receptor and angiotensinogen in preeclamptic placenta / 中华围产医学杂志

Objective To determine the significance of renin angiotensin system (RAS) expressed on placenta in pregnancy induced hypertension (PIH). Methods The expression of placental angiotensin Ⅱtype 1 receptor (AT 1R) and angiotensinogen (AGT) in patients with PIH ( n =20) were investigated and compared with controls ( n =15) using immunohistochemistry and semi quantitative reverse transcription polymerase chain reaction (RT PCR). Results AT 1R was mainly found in the syncytiotrophoblasts, cytotrophoblasts,the vascular endothelial cells and smooth muscle cells. The expression of AT 1R in PIH group (112.43?11.75) was higher than that of control group (170.47? 10.59) ( P

The experimental study of left ventricular assist device on local expression of AngII receptors mRNA of left ventricle in acute left heart failure canine model / 中华胸心血管外科杂志

Objective To evaluate the effect of left ventricular assist device(LVAD) on acute left heart failure canine model by the alteration of local AngII receptor(AT1/AT2) mRNA expression in left ventricular myocytes. Methods 15 canines were randomly divided into 3 groups: Control, hert failure(HF) and HF+LVAD groups. Acute left heart failure model was induced by occluding the left anterior descending coronary artery (LAD) or LAD+left circumflex coronary artery (LCX). The LVAD group was treated for 3 hours by pneumatic LVAD, whose output was 70?ml?kg. -1.?min. -1.. 100mg myocardium was taken from the left ventricle of each dog at 1, 2, 3 hours respectively. The expression of the local left ventricle AngII receptor (AT1/AT2) mRNA was tested by reverse transcription-polymerase chain reaction (RT-PCR). Results When compare with the control group, the expression of the AT1 mRNA in ischemic left ventricle decreased significantly in HF group after heart failure; AT2 mRNA in ischemic left ventricle increased significantly in HF group after heart failure. At 1, 2, 3 hours after LVAD, the AT1 mRNA level of the HF+LVAD group was higher than that of the HF group's, the AT2 mRNA level of the LVAD group was lower than that of the HF group's. Conclusion After heart failure, the expression of AT1 mRNA decreased, but it can be reversed by the LVAD. The expression of AT2 mRNA increased, and it can be reversed by the LVAD. The improvement of the AT1 mRNA and AT2 mRNA values in HF+LVAD group shows the improvement of left ventricular function.

The study on angiotensin converting enzyme and angiotensin type 1 receptor gene polymorphism in patients with vertebro-basilar insufficiency / 中华检验医学杂志

Objective To Investigate the relationship between an in sertion (I)/deletion (D) polymorphism for angiotensin converting enzyme (ACE) and A(1166)C Polymorphism of angiotensin type 1 receptor(AT 1R) genes in patients with vertebro basilar insufficiency(VBI). Methods In this study, We examined 120 patients with VBI and 146 normal controls. The genotype for I/D of ACE and A(1166)C of AT 1R was assessed using polymerase chain reaction (PCR) and refrained fragment length polymorphism(RFLP), respectively. Then we compared the genotype frequency distribution among subjects.Results As a whole, there was significant difference in the distribution of ACE (I/I, I/D and D/D) and AT 1R (A/A and A/C), respectively. D allele frequency was higher in patients compared with the normal controls. Our study also revealed that Ⅱ AA and DD AA genotype frequency in VBI was higher than that in the normal controls.Conclusion The D allele for ACE and C(1166) allele of AT 1R may correlated with VBI.Ⅱ genotype for ACE and AA genotype had a positive con influence on the VBI. The affection of DD AA genotype on VBI was negative.

Effect of telmisartan on the levels of serum adiponectin and C-reactive protein in elderly hypertensive patients with unstable angina pectoris / 中华老年医学杂志

ObjectiveTo determine the effect of telmisartan on the levels of serum adiponectin and C-reactive protein(hs-CRP)in elderly hypertensive patients with unstable angina pectoris. MethodsOne hundred and twenty elderly hypertensive patients with unstable angina pectoris were randomized into two groups, telmisartan(n=60) and perindopril(n=60) groups.The levels of hs-CRP,adiponectin, lipid factors, fasting plasma glucose (FPG), insulin and insulin sensitivity index (ISI) were measured before and 6 months after telmisartan and perindopril treatments.ResultsAt the end of 6 months, the telmisartan group showed more reduction in plasma levels of hs-CRP and more increment in serum adiponectin concentrations and ISI significantly. The frequency of cardiovascular events was significantly lower in the patients of the telmisartan group than that of the perindopril group.ConclusionsCompared with perindopril, telmisartan significantly decreases plasma levels of hs-CRP and increases serum adiponectin concentrations in elderly hypertensive patients with unstable angina pectoris. It also significantly decreases the frequency of cardiovascular events in these patients.

The inhibiting effect of valsartan and spironolactone on cardiac fibrosis in spontaneously hypertensive rats / 中华老年医学杂志

Objective To explore the inhibiting effect of valsartan and spironolactone on cardiac fibrosis and the expression of integrin ? 1 and fibronectin in the heart of spontaneously hypertensive rats. Methods Eighteen 6 week old SHR were randomly divided into 3 groups with 6 in each: SHR control group, valsartan treating group(30 mg?kg -1 ?d -1 ) and spironolactone treating group ( 20 mg?kg -1 ?d -1 ). Six homogenous male WKY rats served as normal group. After 14 weeks of treatment, systolic blood pressure, left ventricular mass, the ratio of left ventricular mass to body weight (LVM/BW), collagen volume fraction(CVF) and perivascular collagen area(PVCA) were determined and compared among these groups. The expression of integrin ? 1 and fibronectin were also examined by immunohistochemical method. Results Compared with the untreated SHR S, systolic blood pressure was significantly decreased in both treatment groups. LVM/BW〔(2 84?0 14)?10 -3 vs(3 22?0 15)?10 -3 〕, CVF〔(3 21?0 22)%vs(4 00?0 28)%〕, PVCA〔(0 62?0 15)%vs(0 94?0 56)%〕 were lower in both treatment groups, these parameters in SHR V group were even lower than those in SHR S group. Compared with the untreated SHR S, the expression of integrin ? 1 was significantly reduced in SHR V group, while the expression of fibronectin was markedly reduced in both treatment groups. Conclusions Both valsartan and spironolactone could control blood pressure, and effectively inhibit the cardiac fibrosis. Valsartan could also inhibit the expression of cardiac integrin ? 1 and fibronectin, which might be the reason that valsartan is better than spironolactone in inhibiting cardiac fibrosis.

Influence of the Angiotensin II AT1 Receptor Antagonist on Reperfusion Injury in Rat Myocardial Ischemia Model

BACKGROUND AND OBJECTIVES: The protective effect of angiotensin converting enzyme (ACE) inhibitor against ischemia/reperfusion injury has been demonstrated in animal models, however the effect of AT1 receptor antagonist is contradictory. The present study was designed to investigate the myocardial protective effects of the AT1 receptor antagonist irbesartan during myocardial ischemia/reperfusion in vivo. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to a 45-minute left coronary artery ligation followed by a 2-hour re-perfusion. An inert vehicle (group I:n=14) or irbesartan (50 mg/kg/day:group II, n=12) was administered for 3 days before coronary occlusion. The ratio of the myocardial infarct area to the ischemic area at risk was assessed through triphenyltetrazolium chloride staining. Apoptosis was evaluated by analyzing DNA fragmentation and TdT-mediated dUDP nick end labeling staining. Western blot analysis was performed for MAP Kinases (ERK1/2 and p38) and Bcl-2 and Bax. RESULTS: The ratio of the infarct area to the ischemic area at risk of group II was smaller than that of group I (42.6+/-2.7% vs. 64.1+/-4.6%;p<0.005). Agarose gel electrophoresis revealed discrete DNA laddering in the ischemic zone of group I, however DNA ladder formation was attenuated in group II. The expressions of ERK1 MAPK and Bcl-2 were increased in the ischemic area of group II compared to that of group I. CONCLUSION: AT1 receptor antagonist was effective in reducing myocardial reperfusion injury in vivo. This effect can at least be partially attributed to the attenuation of cardiomyocyte apoptosis, and this anti-apoptotic effect appears to be related to the increased expression of Bcl-2 and alterations in MAP kinase signaling.

The effect of irbersartan on the osteopontin and MCP-1 expression in lipid-induced renal injury / 中华老年医学杂志

Objective To investigate the expression of osteopontin(OPN) and monocyte chemoattractant protein-1(MCP-1) and the effect of Irbersartan on them in diet-hypercholesterolemia rats. Methods Wistar rats were divided into three groups: normal control rats(C), cholesterol fed rats(H) and cholesterol fed rats treated with Irbesartan(50 mg ? kg -1 ? d -1 ). Twelve weeks later, we measured the 24 hours total urine protein, creatinine clearance and total serum cholesterol, LDL- cholesterol, HDL- cholesterol and triglycerides. Kidney pathology was observed. Immunohistochemistry was used to analyse the expression of OPN, MCP-1, ED1 +and their relationship. Results (1) Total serum cholesterol, LDL-cholesterol level and 24 h total urine protein in H group rats were higher than that in C group rats, there was no significant difference between two groups in HDL-cholesterol and triglycerides.(2) Compared with C group rats , the expression of OPN and MCP-1 increased in cortical tubular epithelium (2.34?0.25 vs 0.49?0.11; 1.93?0.21 vs 0.49?0.11, P

Renoprotective properties of L-158809 in type 2 diabetic rat model / 中华内分泌代谢杂志

Objective To observe the renoprotective effects of angiotensin Ⅱ (ATⅡ) receptor antagonist, L-158809 and to explore its potential mechanisms. Methods The experimental rats consisted of normal control and type 2 diabetic model groups with or without treatment of L-158809 (2 mg?kg -1 ?d -1 ) for 16 weeks. Blood glucose, HbA 1c , serum immunoreactive insulin, serum creatinine, mean arterial blood pressure, creatinine clearance (Ccr) and urinary albumin excretion index (UAEI) as well as plasma and renal ATⅡ content were measured. The kidney morphological changes were examined by renal histopathology. Marix metalloproteinase-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in renal tissues were studied by immunohistochemistry, zymography and Western blot. Results In type 2 diabetic rats, L-158809 restored the blood pressure (P

Role of renin-angiotensin system in the kidney ischemic injury induced by renovascular hypertension / 中国病理生理杂志

AIM: To investigate the role of angiotensin II (Ang II)and Ang II receptor (Ang II R) in the ischemic injury of kidney.METHODS: The expression of renal Ang II type 1 receptor (AT 1R) gene in renovascular hypertensive rats was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and levels of Ang II in the kidney and plasma were examined by radioimmunoassay.RESULTS: The study showed that the contents of Ang II in plasma and renal tissue in experimental group were increased signifiantly ( P

Effects of angiotensin II receptor antagonist on remodeling of renal arterioles in hypertension / 中国病理生理杂志

AIM: To investigate the effects of angiotensin II receptor antagonist on remodeling of renal arterioles in hypertension. METHODS: Eighteen 4 weeks old male rats were divided into three groups: Wistar-Kyoto rats (WKY) for normotensive group, and spontaneously hypertensive rats (SHR) for hypertensive group, and SHR treated with losartan orally (15 mg?kg -1 ?d -1 ). The rats were raised to 16 weeks old. The morphometric parameters of the renal arterioles, and the widths of vascular smooth muscle cells (VSMC) and intercellular space were studied on kidney slices by light microscope and electromicroscope respectively, combined with computer-assistant image analysis system. The minimal renal vascular resistance (RVR min ) was studied by isolated kidney perfusion system. RESULTS: The systolic blood pressure of the tail artery, wall thickness, wall area, ratio of wall thickness to inner diameter, width of VSMC of renal arterioles and RVR min were all smaller or lower in losartan group than those of SHR. CONCLUSION: Ang II receptor antagonist losartan can prevent the remodeling of renal arterioles in SHR.