benazepril and Kidney-Diseases

This multicentre, double-blind, trial in subjects with severe hypertension compared the efficacy and tolerability of two parallel drug regimens: A/B (amlodipine/benazepril: 5/20 or 10/40 mg daily, if necessary) with A (amlodipine: 5 or 10 mg daily, if necessary). The principal dependent variable was the proportion of patients achieving goal blood pressures (BP<140/90 mm Hg or BP<130/80 mm Hg in diabetes or chronic kidney disease) in the two groups within 6 weeks. In the 259 randomized subjects, BP control rates were higher with A/B at 2, 4 and 6 weeks (10.5, 22, and 33.6%, respectively) compared with A (5.7, 16, and 25.8 %, respectively). Corresponding trended BP reductions from baseline at 2, 4 and 6 weeks were about 5 mm Hg greater with A/B (-21+/-16, -26+/-17 and -30+/-17 mm Hg, respectively, compared with A (-16+/-17, -23+/-18 and 25+/-19 mm Hg, respectively, P<0.01). Both regimens were well tolerated; incidences of peripheral oedema at weeks 4 and 6 were similar (A/B: 13 and 20% versus A: 20 and 22%, P=not significant). We conclude that titration of amlodipine and benazepril in single-pill combinations is more effective than titration of amlodipine alone for rapid BP control in patients with severe hypertension.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Benzazepines; Chronic Disease; Diabetes Complications; Drug Therapy, Combination; Edema; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Treatment Outcome; Young Adult

This open, prospective, randomized trial aimed to assess the effects of statins in chronic kidney disease patients on optimized antiproteinuric treatment with combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade.. After 1-month benazepril therapy followed by 1-month benazepril-valsartan combined therapy (run-in), 186 consenting patients with residual proteinuria >0.5 g/24 h were randomized to 6-month benazepril-valsartan therapy alone or combined with fluvastatin. Between-groups changes in proteinuria (primary outcome), serum lipids, and GFR were compared by ANCOVA. Analyses were blinded and by intention to treat.. During the run-in, proteinuria decreased more on benazepril-valsartan than on benazepril alone. Proteinuria reduction correlated with concomitant reduction in total, LDL, and HDL cholesterol, and apolipoprotein B and apolipoprotein A levels. After randomization, median proteinuria similarly decreased from 1.2 (0.6 to 2.2) to 1.1 (0.5 to 1.7) g/24 h on fluvastatin and from 1.5 (0.8 to 2.7) to 1.0 (0.5 to 2.4) g/24 h on benazapril-valsartan therapy alone. Fluvastatin further reduced total and LDL cholesterol and apolipoprotein B versus benazepril-valsartan alone, but did not affect serum triglycerides and GFR. Treatment was well tolerated.. In chronic kidney disease patients with residual proteinuria despite combined angiotensin-converting enzyme inhibitor and angiotensin receptor blockade therapy, add-on fluvastatin does not affect urinary proteins, but further reduces serum lipids and is safe. Whether combined angiotensin-converting enzyme inhibitor, angiotensin receptor blockade, and statin therapy may improve cardiovascular outcomes in this high-risk population is worth investigating.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Chi-Square Distribution; Chronic Disease; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Italy; Kidney Diseases; Lipids; Male; Middle Aged; Prospective Studies; Proteinuria; Renin-Angiotensin System; Tetrazoles; Time Factors; Treatment Outcome; Valine; Valsartan

To investigate the effects of benazepril and heparin on renal function and blood pressure in dogs with chronic kidney disease.. Randomized controlled clinical trial.. 26 dogs with chronic kidney disease.. Dogs were randomly assigned to receive benazepril hydrochloride (0.5 mg/kg [0.23 mg/lb], PO, q 24 h; n = 10), benazepril and heparin (150 U/kg [68 U/lb], SC, q 8 h, for the first 6 days; 10), or a placebo (6) and were followed up for 180 days.. Health status score at the end of the study (ie, day 180) was significantly higher for dogs in the 2 treatment groups than for dogs in the placebo group. In addition, glomerular filtration rate was significantly increased and the urine protein-to-creatinine ratio was significantly decreased, compared with baseline rates, at the end of the study for dogs in both treatment groups but not for dogs in the placebo group. Systolic and diastolic blood pressures were significantly decreased on day 6 for dogs in both treatment groups.. Results suggested that administration of benazepril had beneficial effects in dogs with chronic kidney disease but that short-term administration of heparin in conjunction with benazepril did not appear to provide any additional benefit.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anticoagulants; Azotemia; Benzazepines; Blood Cell Count; Blood Chemical Analysis; Blood Pressure; Blood Urea Nitrogen; Chronic Disease; Creatinine; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Hematologic Tests; Heparin; Kidney; Kidney Diseases; Male; Treatment Outcome; Ultrasonography; Urinalysis

Evidence suggests that transforming growth factor-beta1 (TGF-beta(1)) is associated with target organ damage in hypertension. This study aimed to investigate the relationship between TGF-beta(1) levels and kidney damage and renoprotective effects of angiotensin-converting enzyme inhibitor and/or angiotensin II type 1 receptor blocker in patients with essential hypertension (EH).. A total of 156 patients with EH were enrolled and grouped according to albumin-to-creatinine ratio (ACR). Of these, 90 patients with EH underwent a 12-week antihypertensive trial with administration of benazepril, valsartan or both. Serum TGF-beta(1), plasma angiotensin (Ang) II and urinary albumin were quantified by immunoassays.. Serum TGF-beta1, plasma Ang II and ACR were highly elevated in patients with EH (P < 0.01). There was a positive correlation between serum TGF-beta1 levels and ACR (r = 0.53, P < 0.01). Significant decreases in TGF beta1 and ACR were obtained in all groups at the end of 12-week antihypertensive therapy compared to the baseline values, with the combined group to a greater extent (P < 0.01). Plasma Ang II levels were significantly decreased in the benazepril group but increased in the valsartan group (P < 0.05) while no significant change was observed in the combined group.. TGF-beta(1) is highly elevated and strongly associated with urinary albumin excretion in patients with EH. Treatment with benazepril or valsartan attenuates serum TGF-beta(1) levels and microalbuminuria with the combined therapy receiving the greater effect. TGF-beta(1) could be a potential surrogate marker in monitoring the development and progression of kidney damage in EH.

Topics: Administration, Inhalation; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Double-Blind Method; Female; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Prospective Studies; Tetrazoles; Transforming Growth Factor beta1; Valine; Valsartan

The present study examined the effects of benazepril, an angiotensin-converting enzyme inhibitor, on the progression of renal insufficiency in patients with non-diabetic renal disease.. Fifteen patients with non-diabetic renal disease whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dL were given either benazepril (2.5-5 mg) or placebo once daily for 1 year in a random crossover manner. In both periods, antihypertensive medications were increased if blood pressure was greater than 130/85 mmHg. Blood sampling and urinalysis were performed bimonthly throughout the study period.. Blood pressure was similar when comparing the benazepril and the placebo periods (128+/-12/83+/-6 vs 129+/-10/83+/-7 mmHg). Serum Cr significantly increased from 1.62+/-0.18 to 1.72+/-0.30 mg/dL (P=0.036) during the placebo period, while there was no statistically significant increase in serum Cr during the benazepril period (from 1.67+/-0.17 to 1.71+/-0.27 mg/dL). The slope of decrease of the reciprocal of serum Cr was steeper in the placebo period than in the benazepril period (-0.073+/-0.067 vs-0.025+/-0.096/year, P=0.014). Urinary protein excretion was lower during the benazepril period than during the placebo period (0.57+/-0.60 vs 1.00+/-0.85 g/gCr, P=0.006). Serum K was significantly higher in the benazepril period than in the placebo period (4.4+/-0.5 vs 4.2+/-0.5 mEq/L, P<0.001), but no patient discontinued benazepril therapy as a result of hyperkalemia.. Long-term benazepril treatment decreased the progression of renal dysfunction in patients with non-diabetic renal disease by a mechanism that is independent of blood pressure reduction.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Creatine; Cross-Over Studies; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Proteinuria; Renal Insufficiency

The combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonist (ARB) could provide a higher degree of blockade of the renin-angiotensin system(RAS) than either agent alone. The primary aim of this study was to look at the effect of three therapeutic regimens (titrated ACE inhibitor (ACE-I) versus titrated ARB versus the combination of an ACE-I and an ARB) on the attainment of adequate blood pressure (BP) control and antiproteinuric effect. Both ACE-I and ARB were titrated as monotherapy up to the maximal recommended dose.. A pilot randomised, parallel group open-label study was conducted in 36 patients with primary renal disease, proteinuria above 1.5 g/day and BP >140/90 mmHg while on therapy with an ACE-I. Patients were randomly assigned to (1) benazepril, n=12; (2) valsartan, n=12; or (3) benazepril plus valsartan, n=12. Other antihypertensive therapies could also be added to attain goal BP (<140/90 mmHg). The primary endpoint was the change in proteinuria during six months of follow-up.. In the presence of similar BP decreases and stable creatinine clearance values, mean proteinuria decreases were 0.5+1.7, 1.2+2.0 and 2.5+1.8 g/day in groups 1, 2 and 3, respectively. When compared with baseline values, only the fall induced by the combination of ARB and ACE-I attained statistical significance (p<0.05).. The antiproteinuric capacity of monotherapy at recommended doses with either an ACE-I or an ARB is lower than that obtained with the combination of the two drugs.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Drug Therapy, Combination; Female; Humans; Kidney Diseases; Male; Middle Aged; Pilot Projects; Proteinuria; Tetrazoles; Treatment Outcome; Valine; Valsartan

A protective effect of angiotensin-converting enzyme (ACE) inhibitors has been shown in patients with diabetic nephropathy but has not been clearly established in nondiabetic renal disease. A multicenter European study was designed to determine whether the ACE inhibitor benazepril was safe and effective in protecting residual renal function in patients with various renal diseases and mild to moderate renal failure. The trial involved 583 patients from 49 centers in Italy, France, and Germany. The patients were randomized to receive benazepril or placebo plus other antihypertensive agents, the target being a diastolic blood pressure of less than 90 mm Hg. Thirty-one patients in the benazepril group and 57 patients in the placebo group reached the end point [the time elapsed from entry to (a) doubling of serum creatinine (SCr) concentrations and (b) start of renal replacement therapy; p < 0.001 at 3 years]. The associated reduction in the relative risk of reaching the end point was 53% in benazepril-treated patients, with actuarial renal survival probability significantly better at 3 years. The best survival of renal function was observed in patients with chronic glomerular diseases and proteinuria greater than 1.0 g/24 h. Benazepril is effective in slowing the rate of progression and improving the survival of renal function in patients with renal diseases of various origins. This protective effect is associated with a clinically relevant decrease in both blood pressure and proteinuria.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Creatinine; Female; Humans; Kidney Diseases; Male; Placebos; Prospective Studies; Proteinuria; Renal Insufficiency

Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases.. In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis.. At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group.. Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Disease Progression; Double-Blind Method; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

Topics: Adolescent; Adult; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Female; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies

To observe the effect of Shenkang Injection on the blood pressure, metabolism, blood biochemistry and renal pathology in hypertension renal damge rats, then to provide theoretical basis for clinical trials.. 75 spontaneously hypertensive nephropathy rats were randomly divided into five groups with 15 rats in each group: model group (SHR group) rats were intragastrically treated with the vehicle (4 mL/kg normal saline per day) of Shenkang Injection per day; Benazepril group( positive control group, 8 mg/ kg Benazepril per day) ;Shenkang Injection low-dose group (6.7 mL/kg Shenkang Injection per day); middle-dose group (13.3 mL/kg Shenkang Injection per day); high-dose group (26.6 mL/kg Shenkang Injection per day); and WKY rats were normal control group (n = 15) (4 mL/kg normal saline per day).. After 3 months intraperitoneal injection treatment, SHR rats blood pressure were in- hibited; the levels of microalbumin (m-ALB), total protein (U-TP), serum creatinine (Ser) and urea nitrogen (BUN) were decreased significantly in Shenkang Injection treated groups rats. Shenkang Injection significantly improved the levels of creatinine clearance rate (Ccr), serum albumin (ALB) and superoxide dismutase (SOD), decreased the content of methane dicarboxylic aldehyde (MDA), aldosterone (Ald), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and C-reactive protein (CRP), and had histologic improvement compared with model group.. Shenkang Injection can improve the kidney function, decrease the levels of serum inflammatory factors,improve the oxidative status and reduce the degree of hypertensive renal damage.

Topics: Animals; Benzazepines; Blood Pressure; C-Reactive Protein; Disease Models, Animal; Drugs, Chinese Herbal; Hypertension; Interleukin-6; Kidney; Kidney Diseases; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

The Connectivity Map database contains microarray signatures of gene expression derived from approximately 6000 experiments that examined the effects of approximately 1300 single drugs on several human cancer cell lines. We used these data to prioritize pairs of drugs expected to reverse the changes in gene expression observed in the kidneys of a mouse model of HIV-associated nephropathy (Tg26 mice). We predicted that the combination of an angiotensin-converting enzyme (ACE) inhibitor and a histone deacetylase inhibitor would maximally reverse the disease-associated expression of genes in the kidneys of these mice. Testing the combination of these inhibitors in Tg26 mice revealed an additive renoprotective effect, as suggested by reduction of proteinuria, improvement of renal function, and attenuation of kidney injury. Furthermore, we observed the predicted treatment-associated changes in the expression of selected genes and pathway components. In summary, these data suggest that the combination of an ACE inhibitor and a histone deacetylase inhibitor could have therapeutic potential for various kidney diseases. In addition, this study provides proof-of-concept that drug-induced expression signatures have potential use in predicting the effects of combination drug therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Cell Line, Tumor; Drug Synergism; Drug Therapy, Combination; Gene Expression Profiling; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Kidney; Kidney Diseases; Male; Mice; Vorinostat

To study the renal protective effect of Xinganbao Capsule on rats with adriamycin induced nephropathy (AIN).. Forty male SD rats were randomly divided into four groups, i.e., the normal control group (N), the AIN model group (M), the Benazepril group (B),and the Xinganbao Capsule group (X). AIN rat model was established by left unilateral nephrectomy and repeated caudal vein injection of adriamycin. Gastric perfusion of xinganbao Capsule (at the dose of 500 mg/kg per day) and Benazepril (at the dose of 4 mg/kg per day) was given to rats in the X group and the B group respectively one week after nephrectomy. Rats were sacrificed at the 8th week after medication. The 24-h urinary protein excretion (24 h-UP) and blood biochemical indices were determined. Renal tissues were collected for pathological changes under light and electron microscopes. Expressions of fibronection (FN), collagen IV (COL-IV), and osteopontin (OPN) in renal tissues were detected by immunohistochemistry. mRNA levels of transforming growth factor-beta 1 (TGF-beta1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and plasminogen activator inhibitor-1 (PAI-1) were measured by fluorescent Real-time PCR.. When compared with the model group, 24 h-UP, blood urea nitrogen (BUN), and serum creatinine (SCr), and blood lipids levels were significantly lowered in the X group. The mesangial matrix percentage was less in the X group than in the M group. Renal FN, COL-IV, and OPN expressions more significantly decreased in the X group than in the M group. Similarly mRNA expressions of TGF-beta1,, TIMP-1, PAl-1 in renal tissues obviously decreased.. Xinganbao Capsule could exert its renal protective action possibly through reducing the urinary protein excretion, correcting lipid metabolic disturbance, inhibiting excessive accumulation of extracellular matrix, decreasing the expression of fibrosis factors, and improving the pathological damage of kidneys in the AIN rat model.

Topics: Animals; Benzazepines; Doxorubicin; Drugs, Chinese Herbal; Fibrosis; Kidney; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley

1. Advanced glycation end-products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR). 2. Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar-Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H(2)O(2)-based hydroxyl radical-detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)-kappaB p65, phosphorylated (p-) NF-kappaB p65, vascular cell adhesion molecule (VCAM)-1 and transforming growth factor (TGF)-beta1 was determined by immunohistochemistry, quantitative real-time polymerase chain reaction and western blot analysis. 3. Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF-kappaB p65, p-NF-kappaB p65, VCAM-1 and TGF-beta1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats. 4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Disease Models, Animal; Female; Glycation End Products, Advanced; Hypertension; Kidney Cortex; Kidney Diseases; Male; NADPH Oxidases; Oxidative Stress; Phosphorylation; Platelet-Derived Growth Factor; Proteinuria; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Signal Transduction; Transcription Factor RelA; Transforming Growth Factor beta1; Vascular Cell Adhesion Molecule-1

The effects of iptakalim, a new ATP-sensitive potassium channel opener, were studied in spontaneously hypertensive rats (SHR). Treatment of 12-week-old male SHR (six animals in each group) with iptakalim by gastric lavage at doses of 1, 3, or 9 mg/kg/day for 12 weeks resulted in a lowering of blood pressure. Iptakalim provided significant renoprotection to SHR rats as measured by decreased proteinuria and improved renal function. Histological evidence demonstrated that iptakalim could reverse renal vascular remodeling (of afferent arterioles, arcuate arteries, or interlobular arteries), and improve pathological changes of glomerular, renal interstitial, and glomerular filtration membranes. These effects were accompanied by the decreased circulation and intrarenal concentrations of endothelin 1 and transforming growth factor beta1 (TGF-beta1), and down-regulated overexpression of genes for ET-1, endothelin-converting enzyme 1, TGF-beta1, and the subunits of ATP-sensitive potassium channels (K(ATP)), Kir1.1 and Kir6.1, in the kidney during hypertension. Abnormal expression of matrix components [collagen IV, fibronectin, matrix metalloproteinase 9 (MMP-9) and MMP tissue inhibitor 1 (TIMP-1)] was also significantly reversed by iptakalim. Our results demonstrate that chronic treatment with iptakalim not only reduces blood pressure but also preserves renal structure and function in SHR. In addition to reducing blood pressure, the renoprotective of iptakalim may be involved in inhibiting the circulation and intrarenal concentrations of endothelin 1 and TGF-beta1, regulating the expression of K(ATP) genes and correcting MMP-9/TIMP-1 imbalance in renal tissue, which may result in reducing the accumulation of extracellular matrix molecules.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; ATP-Binding Cassette Transporters; Benzazepines; Endothelin-1; Extracellular Matrix; Hemodynamics; Hypertension; Immunohistochemistry; KATP Channels; Kidney; Kidney Diseases; Kidney Function Tests; Potassium Channels, Inwardly Rectifying; Propylamines; Rats; Rats, Inbred SHR; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta; Transforming Growth Factor beta1

Matrine has an anti-fibrosis effect, such as hepatic cirrhosis and derma fibrosis, while its effect on glomerulosclerosis is unknown. The purpose of this study was to analyze the renoprotective effects of matrine on experimental glomerulosclerosis in rats and inquire into its mechanisms.. The rats were randomly assigned to following groups: normal control group, model control group, benazepril treatment group, matrine 100 mg/kg treatment group and matrine 50 mg/kg treatment group. The rats of normal control group were subjected to sham operation and were injected with normal saline via the tail vein one week later. The rats of the other groups were uninephrectomized and injected with adriamycin (5 mg/kg) via the tail vein one week later. The dose of benazepril was 6 mg/kg. Both matrine and benazepril were given by gastric perfusion from the first day after the operation. The level of urinary protein was measured at the 2nd, 4th and 6th week after the operation. The serum total protein and albumin, serum creatinine, blood urea nitrogen (BUN) were tested only at the 6th week after operation. Renal pathology changes were evaluated at the 6th week as well. Immunohistochemistry was used to detect the expression of fibronectin (FN), laminin (LN), connective tissue growth factor (CTGF) and transforming growth factor-beta1 (TGF-beta1) in glomeruli.. Matrine and benazepril not only reduced the excretion of urinary protein and the level of serum creatinine and BUN, but also significantly ameliorated glomerular mesangial proliferation and glomerular sclerosis (P < 0.05, respectively). Immunohistochemical staining indicated that there was an increasing FN, LN, CTGF and TGF-beta1 expression in model control group as compared to the three treatment groups (P < 0.05). Matrine 100 mg/kg treatment group and benazepril treatment group showed much more advantages than matrine 50 mg/kg treatment group (P < 0.05), but there was no significant difference between the former two groups (P > 0.05).. Matrine has a renoprotective effect on experimental glomerulosclerosis in rats, the possible mechanism might relate to the reduction of the TGF-beta1 negative function via CTGF, which will inhibit the activation and proliferation of glomerular intrinsic cells, decrease the secretion of ECM accordingly.

Topics: Alkaloids; Animals; Benzazepines; Kidney; Kidney Diseases; Kidney Glomerulus; Matrines; Protective Agents; Quinolizines; Rats; Renal Agents

The administration of an angiotensin-converting enzyme (ACE) inhibitor or an oral adsorbent, AST-120 (Kremezin), prevents the progression of renal failure. This study was designed to determine the additional effects of AST-120 combined with an ACE inhibitor, benazepril, on the progression of renal fibrosis in uremic rats.. 5/6-nephrectomized uremic rats were divided into control uremic rats (CRF group), benazepril-treated uremic rats (CRF+B group) and uremic rats receiving benazepril and AST-120 (CRF+BK group). After 14 weeks of treatment renal function and pathological changes were investigated.. The progression of renal dysfunction was delayed in both the CRF+B and CRF+BK groups as compared with the CRF group. In the CRF+BK group, the level of serum and urinary indoxyl sulfate and the tubular accumulation of indoxyl sulfate decreased. Both the CRF+B and CRF+BK groups showed lower glomerular sclerosis indices than the CRF group. In the CRF+BK group, but not the CRF+B group, the interstitial fibrosis area and the expression of transforming growth factor (TGF) beta1 and tissue inhibitor of metalloproteinases (TIMP) 1 were decreased as compared with the CRF group. Furthermore, the CRF+BK group showed a smaller interstitial fibrosis area and a lower renal osteopontin expression than the CRF+B group.. Combination therapy of benazepril and AST-120 is more effective than benazepril alone in retarding the progression of interstitial fibrosis by reducing the expression of TGF-beta 1, TIMP-1 and osteopontin.

Topics: Adsorption; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Carbon; Cells, Cultured; Disease Progression; Drug Therapy, Combination; Fibroblasts; Fibrosis; Humans; In Situ Hybridization; Indican; Kidney; Kidney Diseases; Male; Nephrectomy; Nephrosclerosis; Osteopontin; Oxides; Rats; Rats, Sprague-Dawley; Sialoglycoproteins; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta; Transforming Growth Factor beta1; Uremia

To determine effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency.. 32 cats.. Renal mass was surgically reduced, and cats were assigned to 1 of 4 eight-cat groups. Group 1 received placebo, whereas groups 2, 3, and 4 received benazepril hydrochloride orally once daily for approximately 6.5 months at the following doses: group 2, 0.25 to 0.50 mg/kg of body weight; group 3, 0.50 to 1.00 mg/kg; and group 4, 1.00 to 2.00 mg/kg. Arterial blood pressures, glomerular filtration rate (GFR), and renal plasma flow were determined before treatment and during the treatment period. Other determinants of renal hemodynamics were measured by use of micropuncture techniques. Renal biopsy specimens were examined microscopically.. Compared with cats that received placebo, mean systolic arterial blood pressure was significantly less and GFR significantly greater in cats that received benazepril. Glomerular capillary pressure and the ratio of efferent to afferent arteriolar vascular resistance were also significantly less in treated cats. However, histologic differences in renal specimens were not detected.. Treatment with benazepril sustained single nephron GFR in remnant nephrons of cats with induced renal insufficiency. Administration of benazepril was also associated with a small but significant reduction in degree of systemic hypertension and an increase in whole kidney GFR. Benazepril may be an effective treatment to slow the rate of progression of renal failure in cats with renal disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Blood Urea Nitrogen; Cat Diseases; Cats; Creatinine; Echocardiography; Female; Glomerular Filtration Rate; Heart Rate; Hypertension, Renal; Kidney Diseases; Male; Random Allocation; Renal Plasma Flow; Telemetry

In order to examine the safety of an angiotensin-converting enzyme (ACE) inhibitor in dogs with impaired renal excretion route, benazepril was administered orally, and plasma concentrations of benazeprilat, the active metabolite of benazepril, were determined in dogs with renal mass reduction (1/4th kidney) created by right-side nephrectomy and ligation of branches of the left renal arteries. Five dogs were administered benazepril orally at a given dose (0.5 mg/kg body weight) and 4 other dogs received 20 times that dose (10 mg/kg body weight) once daily for 15 consecutive days before (intact kidney period) and after (1/4th kidney period) creation of kidney impairment. Six control dogs received surgical treatment, but no drug. After creating a 1/4th kidney, plasma urea nitrogen and creatinine concentrations increased to approximately 30 mg/dl and 2.0 mg/dl, respectively, and renal plasma flow and glomerular filtration rate decreased to 37% and 30% of pre-treatment values, respectively. However, these parameters did not change significantly during the 1/4th kidney period both in the 0.5 mg/kg and 10 mg/kg groups. In the 0.5 mg/kg group, plasma benazeprilat concentrations increased to approximately 20 ng/ml to 340 ng/ml 2 hr after each administration, and there were no significant differences between the plasma benazeprilat concentrations during the intact and 1/4th kidney periods. In the 10 mg/kg group, plasma benazeprilat concentrations varied in the individual dog, but did not increase with the days of administration, and were not significantly different on each administration day between the intact and 1/4th kidney periods in either dose group. The AUCs(0-24) of plasma benazeprilat concentrations determined on the 15th administration day were not different between the intact and 1/4th kidney periods in dogs of either dose group. Plasma ACE activities decreased after drug administration in dogs of both groups. Benazepril seemed to have a high safety, and the adjustment of dosage regimen might not be needed in dogs with mild to moderate renal function impairment because the drug was excreted both from the kidneys and liver.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Dog Diseases; Dogs; Female; Glomerular Filtration Rate; Kidney Diseases; Male

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Child; Female; Hemolytic-Uremic Syndrome; Humans; Kidney Diseases; Proteinuria

To study the expressions of angiotensin II 1A receptor (AT1A) both at the mRNA level and the protein level and their modulation by an angiotensin converting enzyme inhibitor, benazepril, in the renal tubulointerstitial injuries induced by unilateral ureteral obstruction (UUO) in rats.. Six SD rats (UUO-T) were administered benazepril in the drinking water (50mg/L). Additional 6 rats were used as untreated controls (UUO-C). Mean arterial Prossure (MAP) was measured at the 10th day after UUO, and then all animals were sacrificed. The expressions of AT1A were examined both at the mRNA level by in situ hybridization using a subtype-specific probe and at the protein level by an immunohistochemistry methods using AT1 receptor antibody in normal rat kidneys and the obstructed rat kidneys.. MAP was 14.2 +/- 0. 6kPa in the UUO-T and 16.6 +/- 0.7kPa in the UUO-C (P < 0.05). Benazepril slowed the tubulointerstitial fibrosis (TIF) and reduced the expression of AT1A in the renal tubular epithelial cells, the interstitial areas, and the walls of renal arteriole in the UUO-T group.. The increased expressions of AT1A were found in the acute renal tubulointerstitial pathogenesis induced by UUO. Benazepril may retard the progression of TIF and decrease the expression of AT1A in the obstructed kidneys. We conclude that the effects of Ang II on the obstructed kidneys may be due to its binding with AT1A.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Female; Fibrosis; Kidney Diseases; Kidney Tubules; Random Allocation; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Ureteral Obstruction

Nine hypertensive patients with mild to moderate renal dysfunction were entered into a protocol to assess the blood pressure, humoral and renal effects of the angiotensin converting enzyme inhibitor, Benazepril (CGS14824A, 2 to 20 mg twice daily) in patients with hypertension and moderate renal insufficiency (mean creatinine clearance 56 ml/min/1.73 m2). Specifically monitored, prior to and following 12 weeks of Benazepril monotherapy, were plasma renin activity and plasma aldosterone, the clearances of creatinine, Tc99m-diethylenetriaminepentaacetic acid (TC99m-DTPA) and para-amino-hippurate, and the 24-hour urinary excretion of protein. Blood pressure was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed. Mean serum potassium increased from 3.9 to 4.2 mEq/L. Benazepril monotherapy had no adverse renal hemodynamic effect. Benazepril appears to be an effective antihypertensive agent in hypertensive patients with moderately impaired renal function.

Topics: Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Potassium; Renin