Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Heart Failure ; drug therapy ; Humans ; Renin-Angiotensin System ; drug effects

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Antiviral Agents ; therapeutic use ; Biomarkers ; blood ; Biopsy ; Elasticity Imaging Techniques ; Humans ; Liver Cirrhosis ; diagnosis ; etiology ; therapy

BACKGROUNDThere have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.

METHODSThis study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.

RESULTSMedian follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.

CONCLUSIONThe results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Heart Failure ; drug therapy ; Humans ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Benzimidazoles ; therapeutic use ; Hypertension ; blood ; drug therapy ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; blood ; Random Allocation ; Rats ; Rats, Inbred SHR ; Tetrazoles ; therapeutic use ; Urotensins ; blood

OBJECTIVETo study the effects of angiotensin II receptor blockers (ARB), losartan and irbesartan, on blood pressure and serum uric acid (SUA) level in mild to moderate essential hypertensive patients complicating hyperuricaemia.

METHODSA total of 351 eligible patients were recruited in this multi-center, randomized, double-blind parallel clinical trial. After 1 week screening and a 2 week single-blinded placebo wash-out period, patients were randomly assigned to receive losartan 50 mg (n=76) or irbesartan 150 mg (n=175) once daily for 4 weeks, followed by a double-dose for another 4 weeks in patients whose seated DBP were >or=90 mm Hg or SBP>or=140 mm Hg at the end of 4 weeks. The SUA concentration and blood pressure were measured at baseline, 4 and 8 weeks post therapy.

RESULTSThree hundred and twenty-five patients completed the study (162 in the losartan group and 163 in the irbesartan group). Both groups were well matched for baseline clinical characteristics and demographics. SUA was significant reduced in losartan group (430.93 micromol/L vs 372.35 micromol/L, P<0.0001), but not in Irbesartan group (430.46 micromol/L vs 420.67 micromol/L, P>0.05) 8 weeks post therapy compared to baseline level. Blood pressure was significantly and equally reduced in both groups after 8 weeks treatment compared to baseline level (P<0.0001).

CONCLUSIONLosartan is an optimum choice of medication for patients with mild-to-moderate hypertension complicating hyperuricemia.

Adult ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Biphenyl Compounds ; therapeutic use ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Hypertension ; drug therapy ; metabolism ; Losartan ; therapeutic use ; Male ; Middle Aged ; Tetrazoles ; therapeutic use ; Uric Acid ; metabolism

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Gastric Mucosa ; blood supply ; pathology ; Hypertension, Portal ; drug therapy ; Male ; Propranolol ; therapeutic use ; Rats ; Rats, Wistar ; Tetrazoles ; therapeutic use ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan

OBJECTIVETo investigate the effects of valsartan on expression of angiotensin II receptors in different regions of heart after myocardial infarction (MI).

METHODSCanines were divided into sham-operated control group (n=7), infarction group (n=7) and Valsartan group (10 mg x kg(-1) x day(-1) for 4 weeks after MI operation, n=7). Four weeks after operation, Doppler tissue imaging (DTI) was used to evaluate regional ventricular function in the noninfarcted myocardium (apical and basal near to the infarction region). The mRNA and protein expressions of angiotensin II type 1 receptor (AT1-R) and angiotensin II type 2 receptor (AT2-R) on the corresponding regions were detected by competitive reverse-transcriptase polymerase chain reaction technique and immunohistochemical technique respectively. Results The protein and mRNA expressions of AT1-R were significantly increased in both apical and basal regions near to the infarction in dogs with MI compared with those in control group (P < 0.05) which could be downregulated by valsartan (P < 0.05). AT2-R expressions were significantly upregulated in infarction group in both apical and basal regions compared with those in control group and valsartan further increased AT2-R expressions in both areas (P < 0.05). Myocardial peak systolic velocity (Sm), myocardial peak early diastolic velocity (Em) and myocardial peak late diastolic velocity (Am) at both apical and basal regions near to the infarction regions were significantly lower in MI group than those in the control group which could be significantly improved by valsartan.

CONCLUSIONBoth mRNA and protein expressions of AT1-R and AT2-R are upregulated in noninfarcted regions near MI, valsartan improved myocardial function via inhibiting AT1-R upregulation and enhancing AT2-R upregulation.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; therapeutic use ; Animals ; Dogs ; Female ; Male ; Myocardial Infarction ; drug therapy ; metabolism ; physiopathology ; Myocardium ; metabolism ; RNA, Messenger ; metabolism ; Receptor, Angiotensin, Type 1 ; metabolism ; Receptor, Angiotensin, Type 2 ; metabolism ; Tetrazoles ; pharmacology ; therapeutic use ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan

Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Chronic Disease ; Drug Therapy, Combination ; Humans ; Hypertension ; drug therapy ; Kidney Diseases ; drug therapy ; Proteinuria ; drug therapy

OBJECTIVETo evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor (AT-1 receptor) blocker on the progression of rat pulmonary fibrosis induced by bleomycin A5.

METHODSTwenty-four male Wistar rats were randomized into pulmonary fibrosis model, perindopril treatment, losartan treatment and control groups. In the former 3 groups, pulmonary fibrosis was induced via intratracheal injection of bleomycin A5 (5 mg/kg), after which the rats in the perindopril and losartan groups received intragastric administration of the corresponding agents at the daily dose of 2 mg/kg and 10 m/kg, respectively. The rats in the control group had intratracheal injection of normal saline only. In the 4th week, the histological changes of the lung tissues were examined microscopically with Masson staining. Hydroxyproline content in the lungs was measured, and the protein expressions of AT-1 receptor, TGF-beta1 and IkappaBalpha were examined using Western blotting. DNA binding activity of NF-kappaB was analyzed with electrophoretic gel mobility shift assay (EMSA), and zymography was used to assess the activity of matrix metalloproteinase-2 and 9 (MMP-2, 9).

RESULTSBoth perindopril and losartan treatment significantly reduced the pulmonary fibrosis score, content of hydroxyproline, protein expression of TGF-beta1, DNA binding activity of NF-kappaB and MMP-2, 9 activity, and increased cytoplasmic protein expression of IkappaBalpha. Perindopril treatment lowered the protein level of AT-1 receptor.

CONCLUSIONPerindopril and losartan may inhibit bleomycin A5-induced pulmonary fibrosis in rats by reducing the protein expression of TGF-beta1 and suppressing the DNA binding activity of NF-kappaB and MMP-2, 9 activity.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Animals ; Bleomycin ; analogs & derivatives ; Blotting, Western ; Losartan ; therapeutic use ; Male ; NF-kappa B ; metabolism ; Perindopril ; therapeutic use ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo observe the effects of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats.

METHODSExcept rats in the control group, all were given intraperitoneal injections of 1% dimethylnitrosamine (DMN 1 ml/kg, two or three consecutive days/a week for 6 weeks). From the first day of the intraperitoneal injection, rats in treatment groups were given valsartan for 8 weeks by gastric gavage. Liver tissue and blood samples of all rats were examined at 56 days (8 weeks). AngII levels were determined by radioimmunoassay. Hepatic mRNA levels of Collagen type I (Col I) and tissue inhibitor of metalloproteinase1 (TIMP1) were evaluated by reverse-transcription polymerase chain reaction (RT-PCR).

RESULTSValsartan significantly attenuated the degree of liver fibrosis and decreased the hepatic AngII content compared with DMN treated rats (P<0.01). mRNA levels of Col I and TIMP1 were upregulated in DMN treated rats compared with normal rats. Valsartan downregulated the elevation of Col I and TIMP1 mRNA levels (P<0.01).

CONCLUSIONHepatic AngII content of the model group was increased, the local tissue RAS was activated in DMN induced liver fibrosis. Valsartan can retard the progression of hepatic fibrosis and may provide an effective new strategy for anti-liver fibrosis therapy.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; therapeutic use ; Animals ; Dimethylnitrosamine ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; prevention & control ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Tetrazoles ; pharmacology ; therapeutic use ; Valine ; analogs & derivatives ; pharmacology ; therapeutic use ; Valsartan