benazepril and Fibrosis

To explore the effect of simvastatin on myocardiac fibrosis in patients with essential hypertension (EH).. Sixty EH patients were randomly assigned into 2 groups: Benazepril (10 mg/d) group (n = 28) and simvastatin (20 mg/d) + benazepril (10 mg/d) group. Procollagen type III aminoterminal peptide (PIIIP), and procollagen type IV aminoterminal peptide (PIVP) levels in serum as well as transforming growth factor beta 1 (TGFbeta1) level in plasma were measured by radioimmunoassay (RIA) before and 6 months after the treatment. Doppler ultrasound recordings were obtained from all patients before and 6 months after the treatment to determine several parameters related to the left ventricular anatomy and function.. After 6 month of treatment, the mean blood pressure (MBP), PIIIP, PIVP, TGFbeta1, left ventricular mass index (LVMI), interventricular spectum dimension (IVSD), and left ventricular posterio wall dimension (LPWD) in the 2 groups were significantly lower than those before the treatment. TGFbeta1 decreased in the simvastatin and benazepril group compared with the benazepril group (P < 0.01). The ratio of early diastolic blood flow velocity of mitral valve (VE) and blood flow velocity of atrium systolic period (VA) in the 2 groups significantly increased after 6 months of treatment, and the ratio in the simvastatin and benazepril group was significantly higher than that in the enazepril group (P < 0.05).. Angiotension converting enzyme inhibitor combined with simvastatin is helpful to reduce the myocardial fibrosis and to improve the left ventricular hypertrophy and diastolic function in EH patients.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Drug Therapy, Combination; Female; Fibrosis; Humans; Hypertension; Male; Middle Aged; Myocardium; Simvastatin

LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNi), is reported to play a cardioprotective role after acute myocardial infarction (AMI). Angiotensin-converting enzyme inhibitors(ACEIs) have similar roles. However, it is unclear whether the combination of the two drugs has a better protective effect. The purpose of this study was to investigate the effect of this combination therapy after AMI.. Male C57BL/6 J mice subjected to ligation of left anterior descending artery were treated for 4 weeks with LCZ696, ACEI(benazepril), or both(combination therapy) after induction of MI. Cardiac function, hemodynamics, and inflammatory factors were evaluated at 1 st day, 14th day, and 28th day. Heart weight and myocardial fibrosis were measured at the end of the experiment.. Blood pressure was lower in all treatment groups than in the control group. The combination therapy group had the strongest antihypertensive effect. Compared with LCZ696 or benazepril, treatment with combination therapy increased ejection fraction, fractional shortening, and cardiac output and decreased N-terminal pro-B-type natriuretic peptide(NT-proBNP). The ratios of heart weight to body weight in all treatment groups were less than that in the control group. Compared with the control and LCZ696 group, the fibrotic area in the combination therapy group was suppressed and had a lower level of TGF-β1 in the left ventricle. The plasma concentration of bradykinin and renin in the combination therapy group were highest among groups at 14th and 28th day.. LCZ696 in combination with benazepril showed better positive effects in modulating heart failure and myocardial fibrosis after acute AMI in mice and affect some inflammatory markers.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Biphenyl Compounds; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Fibrosis; Heart Failure; Hemodynamics; Inflammation Mediators; Male; Mice, Inbred C57BL; Myocardial Contraction; Myocardial Infarction; Myocardium; Neprilysin; Protease Inhibitors; Renin; Tetrazoles; Transforming Growth Factor beta1; Valsartan; Ventricular Function, Left

To compare the potential beneficial effects of the angiotensin converting enzyme inhibitor (ACEI) benazepril and the angiotensin II receptor 1 blocker (ARB) irbesartan on vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats (SHRs).. Twelve-week-old female SHRs were treated with irbesartan or benazepril for 12 weeks. Vaginal renin angiotensin system (RAS) components were detected by polymerase chain reaction and western blot and vaginal α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), and collagen III (Col III) were analyzed by western blot. Vaginal tissue sections were examined by hematoxylin and eosin staining, Masson trichrome staining, and immunohistochemical analysis of α-SMA and Col III.. Irbesartan and benazepril had different impacts on vaginal RAS components. Both agents decreased vaginal α-SMA and Col III and increased eNOS expression in SHR. The wall/lumen thickness ratio of vaginal arterioles was similarly decreased following irbesartan and benazepril treatment. Both drugs also decreased collagen deposition in SHRs. There was no difference in vaginal vascular remodeling or fibrosis between the two groups.. Irbesartan and benazepril have different effects on vaginal RAS expression but similar positive effects against vaginal vascular remodeling and fibrosis.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Female; Fibrosis; Hypertension; Irbesartan; Rats; Rats, Inbred SHR; Tetrazoles; Vascular Remodeling

Renal fibrosis is essential for the progression of diabetic nephropathy (DN). Macrophages accumulate in diabetic kidneys and are involved in epithelial-to-mesenchymal transition (EMT), a vital mechanism leading to renal fibrosis. Recently, high-mobility group nucleosome-binding protein 1(HMGN1) was documented in promoting the recruitment and activation of antigen-presenting cells. In this study, we first reported its roles in renal fibrosis and the underlying mechanism associated with macrophage filtration and EMT.. Twenty C57BL/6J mice were administered streptozotocin (STZ) to induce diabetes for 6 weeks and then divided into 4 groups: normal control group; DN group; benazepril-treated group, and insulin-treated group. Blood glucose, creatinine, and albumin in urine, hematoxylin and eosin, and Sirius red staining of kidney tissues were used to assess the renal pathology. ELISA, immunochemistry, and in situ hybridization were performed to determine the expression of HMGN1, CD68, F4/80, α-smooth muscle actin, and E-cadherin.. The renal expression levels of HMGN1, macrophage markers, and EMT makers were increased in DN group, and insulin treatment could reduce the overexpression of these indicators with a better effect than benazepril treatment. Both treatments could not obviously ameliorate urine albumin-to-creatinine ratio, collagen expression, and renal histological changes in STZ-induced diabetic mice. Correlation analysis indicated that there was a relationship among HMGN1, macrophage markers, EMT markers, and collagen expression in DN mice.. HMGN1 may promote macrophages accumulation and EMT, suggesting a potential therapeutic target for preventing renal fibrosis development in DN.

Topics: Animals; Benzazepines; Collagen; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Epithelial-Mesenchymal Transition; Fibrosis; HMGN1 Protein; Insulin; Kidney; Macrophages; Mice; Mice, Inbred C57BL

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

The present study was designed to explore the roles of MMP-2/TIMP-2 in cardiac fibrosis and to study the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI) on cardiac remodelling in streptozotocin(STZ)-induced diabetic rats.. Male Wistar rats were randomly divided into three groups: a normal control group (NC), a diabetes mellitus-untreated group (DM) and a diabetes mellitus benazepril-treated group (DB). Diabetes mellitus was induced in the DM and DB groups by intraperitoneal injection of streptozotocin (60 mg/kg). DB rats were treated with benazepril 10 mg/kg/day for 12 weeks by remedial perfusing of the stomach. In the DM group, compared with the NC group, the gene and protein expression of MMP-2 decreased while the TIMP-2 gene and protein expression increased in heart tissues, along with a markedly cardiac collagen deposition.All the above changes were attenuated by benazepril treatment in the DB group.. The imbalance of MMP-2 and TIMP-2 expressions in heart tissues might participate in interstitial fibrosis in diabetic myocardiopathy. Benazepril may ameliorate cardiac fibrosis partly by regulating the MMP-2/TIMP-2 system.

Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Glucose; Body Weight; Collagen; Diabetes Mellitus, Experimental; Fibrosis; Immunoenzyme Techniques; Male; Matrix Metalloproteinase 2; Myocardium; Organ Size; Random Allocation; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Staining and Labeling; Streptozocin; Tissue Inhibitor of Metalloproteinase-2

Benazepril, an angiotensin-converting enzyme inhibitor, and candesartan, an angiotensin receptor blocker, are common drugs for treating hypertension. This study aimed to investigate the enhanced attenuation of myocardial fibrosis in spontaneously hypertensive rats (SHRs) possibly induced by joint treatment with benazepril and candesartan and the possible involvement of transforming growth factor beta1 (TGF-beta1)-Smad signaling pathway. SHRs were treated with benazepril at 10 mg.kg.d, candesartan at 4 mg.kg.d, and a combination of 2 drugs at half dose, respectively, for 12 weeks. Echocardiography and histology indicated that joint treatment with 2 drugs more significantly inhibited myocardial fibrosis in SHRs than either monotherapy, as evidenced by the changes in cardiac structural parameters, ultrasonic integrated backscatters, collagen volume fraction, and perivascular collagen area. The collagen analyses further revealed that significant decreases in total collagen concentration, the ratio of collagen type I to type III, and collagen cross-linking were found after the enhanced attenuation of myocardial fibrosis. Western blot analysis showed that the protein expression of TGF-beta1 and Smad3 was significantly decreased after joint treatment with 2 drugs. We conclude that synergistic attenuation of myocardial fibrosis in SHRs is produced by combined use of benazepril and candesartan possibly through the modulation of TGF-beta/Smad signaling proteins.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Benzimidazoles; Biphenyl Compounds; Drug Synergism; Drug Therapy, Combination; Fibrosis; Myocardium; Rats; Rats, Inbred SHR; Tetrazoles

Although recent clinical studies have indicated that angiotensin II receptor blocker is as effective in treating heart failure as an angiotensin-converting enzyme inhibitor, it is unknown whether their effects are different. Dahl salt-sensitive rats were treated with an angiotensin-converting enzyme inhibitor benazepril, and an angiotensin II receptor blocker candesartan from 11 weeks old. We examined cardiac geometry and function by echocardiography, and histology and gene expression by high-density oligonucleotide arrays using Affymetrix U34 (Affymetrix, Santa Clara, CA, U.S.A.). Dahl salt-sensitive rats fed a high salt diet showed a marked increase in blood pressure and developed concentric hypertrophy at 11 weeks, followed by left ventricle dilation and congestive heart failure by 20 weeks after birth. Although both medications had only a mild antihypertensive effect, they strongly suppressed the development of cardiac hypertrophy, fibrosis and heart failure to the same extent. Gene expression pattern examined by Affymetrix GeneChip (Affymetrix) is quite different between the two drug groups, indicating that angiotensin II receptor blocker and angiotensin-converting enzyme inhibitor prevent heart failure by different mechanisms.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Benzimidazoles; Biphenyl Compounds; Disease Models, Animal; Echocardiography; Fibrosis; Gene Expression; Gene Expression Profiling; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Infusions, Parenteral; Male; Oligonucleotide Array Sequence Analysis; Organ Size; Rats; Rats, Inbred Dahl; Receptors, Angiotensin; Sodium Chloride, Dietary; Subcutaneous Tissue; Tetrazoles; Time Factors; Ventricular Function, Left

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 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

Converting enzyme inhibitors impair renal function of the kidney beyond a stenosis of the renal artery in humans and induce histological lesions in the clipped kidney of renal hypertensive rats. In two-kidney, one clip hypertensive rats, we compared the time course and magnitude of the biochemical effects of angiotensin converting enzyme inhibition on the plasma renin-angiotensin system, cardiac hypertrophy, renal lesions, and 24-hour blood pressure decrease induced by either intermittent angiotensin converting enzyme inhibition administration (benazepril PO, 10 mg/kg once a day, n = 93) or continuous administration (benazeprilat, 3 mg/kg per day via osmotic pumps, n = 92). Control rats (n = 91) received the drug vehicle intermittently or continuously. Mortality was significantly reduced by both intermittent (n = 3/93) and continuous (n = 3/92) inhibition compared with controls (n = 18/91) (P < .001). Changes in the plasma renin-angiotensin system and blood pressure were parallel. A continuous suppression of the activity of the plasma renin-angiotensin system was associated with a 24-hour decrease in blood pressure with continuous inhibition, whereas intermittent inhibition induced a similar fall in blood pressure only for the first hours after gavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Creatinine; Fibrosis; Heart Rate; Hypertension, Renovascular; Kidney; Male; Myocardium; Organ Size; Rats; Rats, Wistar; Renin; Urea