Aspirin ; therapeutic use ; Bisoprolol ; therapeutic use ; Cardiomyopathies ; chemically induced ; etiology ; Cardiotonic Agents ; adverse effects ; Chest Pain ; diagnostic imaging ; Dobutamine ; adverse effects ; Echocardiography, Stress ; adverse effects ; Enalapril ; therapeutic use ; Humans ; Male ; Middle Aged ; Simvastatin ; therapeutic use

OBJECTIVETo observe the effect of Chinese herbal medicine for calming Gan (肝) and suppressing hyperactive yang (平肝潜阳, CGSHY) on arterial elasticity function and the circadian rhythm of blood pressure in patients with essential hypertension (EH).

METHODSAdopting a parallel, randomized design, sixty-four patients with EH of stages I and II were randomly divided into two groups according to a random number table, with 32 in each group. The patients in the treatment group were treated with CGSHY and those in the control group were treated with Enalapril. All patients were given 24-h ambulatory blood pressure monitoring (ABPM) before and after a 12-week treatment. Trough/peak (T/P) ratios of systolic and diastolic blood pressure (SBP & DBP) of each group were calculated. The circadian rhythm of their blood pressure was observed at the same time. The changes in elasticity of the carotid artery in the patients, including stiffness parameter (β), pressure-strain elastic modulus (Ep), arterial compliance (AC), augmentation index (AI), and pulse wave velocity (PVWβ) were determined by the echo-tracking technique before and after a 12-week treatment. In the meantime, their levels of nitric oxide (NO) and endothelin-1 (ET-1) were measured respectively.

RESULTSAfter treatment, all parameters in the 24-h ABPM and the elasticity of the carotid artery (β, Ep, AC and PVWβ) were markedly improved, the level of NO was increased, and ET-1 was decreased in both groups as compared with values before treatment (P<0.05 or P<0.01). Further, the improvements in the ratio of T/P of SBP & DBP and in the level of NO and ET-1 in the treatment group were more significant than those in the control group (P<0.05). There were no significant differences in all parameters in the ABPM monitoring and the elasticity of the carotid artery, the recovery of blood pressure circadian rhythm, and the therapeutic effect of antihypertension in EH patients between the two groups (P>0.05).

CONCLUSIONSChinese herbal medicine for CGSHY may lower the blood pressure smoothly and recover the circadian rhythm of blood pressure in EH patients. They may also improve the carotid elasticity of EH patients similar to that of Enalapril. The mechanism of action of Chinese herbs on EH might be related to the regulation of vascular endothelium function.

Antihypertensive Agents ; Arteries ; drug effects ; physiopathology ; Blood Pressure ; drug effects ; physiology ; Blood Pressure Monitoring, Ambulatory ; Circadian Rhythm ; drug effects ; physiology ; Drugs, Chinese Herbal ; therapeutic use ; Elasticity ; drug effects ; physiology ; Enalapril ; pharmacology ; therapeutic use ; Endothelin-1 ; metabolism ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Middle Aged ; Nitric Oxide ; metabolism ; Time Factors ; Treatment Outcome ; Yin-Yang

This experiment on rats was aimed to investigate the expression of intermedin (IMD) in hypertrophic cardiac myoctye of renal vascular hypertension induced by incomplete ligation of the left renal artery, and so to detect and compare the changes of the expression after administration of Valsartan, Amlodipine and Enalapril respectively. The criterion for standard modeling was systolic pressure > or = 140 mmHg. At 4 weeks after successful modeling, 60 SD male rats were randomly divided into 5 groups, namely the hypertrophy group, the 3 drug-treatment groups, and the sham-operation group as control. Blood pressure, left ventricular mass index (LVMI), and the left ventricular mean transverse diameter of myocardial cell (LVTDM) were investigated at the 10th week after model establishment. Gene expression of IMD mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the optical density of the band was measured by use of the Gel Documentation System. The ratio of IMD mRNA to beta-actin mRNA was considered the relative amount of IMD. When compared with control, the blood pressure increased significantly in the hypertrophy group. There was no statistically significant difference between the treatment groups. No significant difference in heart rate was noted at 4 weeks after operation in all groups. LVMI and LVTDM levels were significantly higher in the hypertrophy group than in the other groups; LVMI and LVTDM levels showed no significant difference among the treatment groups but they were obviously higher than those of the Sham-operation group. The gene expression of IMD mRNA in the hypertrophy group was upregulated in the myocardium, when compared with that in the other groups. Meanwhile, although IMD mRNA in the treament groups was higher than that in the Sham-operation group, no statistically significant difference of myocardial IMD mRNA was found between the treament groups. These results suggested that, in this experiment, intracardiac IMD mRNA was upregulated and could participate in the regulation of cardiac remodeling in renal vascular hypertension-induced cardiac hypertrophy. This upregulation could improve the pathologic and physiologic process of cardiac hypertrophy, and could associate with the pressure loading or myocardia hypertrophy. However, the change did not display any difference that could be attributed to the variety of hypotensive drugs.
Adrenomedullin ; genetics ; metabolism ; Amlodipine ; therapeutic use ; Animals ; Antihypertensive Agents ; therapeutic use ; Cardiomegaly ; etiology ; metabolism ; Enalapril ; therapeutic use ; Hypertension, Renovascular ; complications ; drug therapy ; metabolism ; Male ; Myocardium ; metabolism ; Neuropeptides ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; therapeutic use ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan

OBJECTIVE: To dynamically observe the effect of enalapril on the expression of transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (alpha-SMA), and Smad7 in the obstructed kidney after unilateral ureteral obstruction (UUO) in rats, and to investigate the effect of enalapril on transdifferentiation of renal tubular epithelial cells. METHODS: The model rats were induced by ligating the left ureter. Male Sprague-Dawley (SD) rats were divided into a normal control (sham-surgery) group, a model group, and a treatment group (enalapril 10 mg/ (kg * d) by gastric gavage from 24 h before the obstruction day). Rats were sacrificed on day 3, 7, 14, 21 after UUO was initiated. Sections of the renal tissue were stained with hematoxylin and eosin stain, which were used for histological and morphometric studies of the pathological change of the obstructed kidney. Real-time PCR was performed to examine the expression of TGF-beta1 mRNA and CTGF mRNA, and Western blot was performed to examine the expression of Smad7, alpha-SMA, and CTGF in the obstructed kidney. RESULTS: The score of renal interstitial lesion increased with the extension of obstruction. The expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF increased in the model group with the extension of obstruction; but Smad7 expression decreased. Compared with the UUO group,the degree of renal interstitial lesion and the expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF were decreased, but the expression of Smad7 increased in the treatment group. Enalapril could significantly decrease TGF-beta1 mRNA on day 3, 7, 14, 21 after UUO. Enalapril could significantly affect the expression of CTGF mRNA,alpha-SMA,CTGF and Smad7 on day 3, 7, 14 after UUO initiation. CONCLUSION Enalapril significantly alleviates renal interstitial fibrosis by suppressing the expression of TGF-beta1, CTGF and alpha-SMA, upregulating the expression of Smad7, and has better effect at early stage (within 14 days after the UUO).
Actins ; genetics ; metabolism ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Animals ; Connective Tissue Growth Factor ; genetics ; metabolism ; Enalapril ; therapeutic use ; Fibrosis ; prevention & control ; Kidney Tubules ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Smad7 Protein ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Ureteral Obstruction ; drug therapy ; metabolism ; pathology

OBJECTIVETo investigate the clinical effect of combined use of enalapril (an angiotensin converting enzyme inhibitor, ACEI) and Bailing Capsule (a Chinese herbal preparation made by fermented cordyceps sinensis, BLC) on renal function in patients with chronic allograft nephropathy (CAN) for seeking an effective therapy to control CAN progression.

METHODSEighty-four CAN patients were randomly assigned to four groups, the 22 patents in group A treated with combined treatment of enalapril (10 mg/d) and BLC (2.0 g, twice a day); 20 in group B with enalapril alone; 21 in group C with BLC alone; and 21 in group D with the previously used immunosuppressive agents for control. Levels of serum creatinine (SCr), blood urea nitrogen (BUN), clearance of creatinine (CCr), 24 h urinary protein (24 h Upro) and urinary transforming growth factor beta1 (TGF-beta1) in all patients were measured before treatment, and after 6-and 9-month treatment.

RESULTSCCr was improved in patients of group A after 6-month treatment accompanied with decrease of SCr, 24 h Upro and urinary TGF-131 (P < 0.05), the latter 3 indexes were lower than in group D, and there was no difference among group A-C. These indexes in patients of group A, B, and C were further improved after treatment for 9 months (P < 0.01), whereas they worsened in patients of group B (P < 0.05). and the cases of patients with renal function improving or stable condition were more in group A than those in group B.

CONCLUSIONCombined treatment of enalapril and BLC has better efficacy than using enalapril or BLC alone in reducing excretion of urinary protein, improving or stabilizing the function of graft kidney, and retarding CAN progression.

Adult ; Aged ; Blood Urea Nitrogen ; Capsules ; Creatinine ; blood ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Enalapril ; therapeutic use ; Female ; Humans ; Kidney Diseases ; blood ; drug therapy ; surgery ; urine ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Proteinuria ; blood ; drug therapy ; Urine ; chemistry ; Young Adult

OBJECTIVE: To investigate the effect of enalapril on renal interstitial fibrosis in rats with unilateral ureteral obstruction(UUO). METHODS: UUO model was induced by ligating the left ureter in rats. Male Sprague-Dawley(SD) rats were randomly divided into a sham-operated group(n=16), a UUO model group(n=24), and an enalapril treated group(n=24). The rats were treated with 10 mg/kg.d by gastric gavage in the enalapril treated group from 24 h before the operation, and the rats were treated with the identical dose of normal saline in the other 2 groups. The rats were sacrificed at 3,7,14, and 21 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the mRNA expression of collagen I (Col I) was detected by real-time PCR, and the protein expression of connective tissue growth factor (CTGF) was detected by Western blot. RESULTS: The renal interstitial damage index, relative collagen area and the expression of Col I mRNA and CTGF in the renal tissues in the model group increased with the prolongation of obstruction. Enalapril significantly reduced the renal interstitial damage index and relative collagen area, and inhibted the expression of Col I mRNA and CTGF. There was significant difference on day 3,7,and 14 (P<0.05), but not on day 21 (P>0.05). CONCLUSION Enalapril significantly attenuates renal interstitial fibrosis by supressing the expression of Col I mRNA and CTGF.
Animals ; Collagen Type I ; biosynthesis ; genetics ; Connective Tissue Growth Factor ; biosynthesis ; genetics ; Enalapril ; therapeutic use ; Male ; Nephritis, Interstitial ; etiology ; prevention & control ; Nephrosclerosis ; etiology ; prevention & control ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications

PURPOSE: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACE-I) in retarding progression of severe non-proliferative diabetic retinopathy (NPDR) in normotensive type 2 diabetic patients. METHODS: This was a retrospective case control study of 128 patients with normotensive type 2 diabetes with lower than +1 dipstick proteinuria and severe NPDR who were classified into either an ACE-I treated group (Enalapril maleate 10 mg, n=12 , Ramipril 5 mg, n=17) or an ACE-I untreated group (n=99). Medical records were reviewed for endpoints of (a) occurrence of proliferative diabetic retinopathy (PDR) or macular edema (ME) for which laser phototherapy was necessary or (b) development of proteinuria of higher than +1 level requiring medication of ACE-I. RESULTS: From the total of 128 patients, there were 29 ACE-I treated patients and 99 ACE-I untreated patients. There were no differences in the average age, duration of diabetes, body mass indices, blood pressure and levels of hyperglycemia or HbA1C between the two groups. Blood pressure and HbA1C levels in both groups remained unchanged during the study. The mean follow-up period was 41.6 months. In the ACE-I group, 6 patients progressed to PDR, 5 to ME and 6 developed proteinuria of greater than +1 over the follow-up period. In the control group, 30 patients progressed to PDR, 6 to ME and 9 developed proteinuria of greater than +1 over the follow-up period. CONCLUSIONS: Small doses of ACE-I did not yield any beneficial effects in retarding the progression of severe NPDR.
Treatment Failure ; Severity of Illness Index ; Retrospective Studies ; Ramipril/administration & dosage/*therapeutic use ; Middle Aged ; Male ; Humans ; Fundus Oculi ; Female ; Enalapril/administration & dosage/*therapeutic use ; Dose-Response Relationship, Drug ; Disease Progression ; Diabetic Retinopathy/*drug therapy/pathology ; Diabetes Mellitus, Type 2 ; Case-Control Studies ; Angiotensin-Converting Enzyme Inhibitors/administration & dosage/*therapeutic use ; Aged

OBJECTIVETo investigate the preventive and therapeutic effects of enalapril maleate (Enalaprilat) (E) on myocardial damage in early stage after burns.

METHODSA total of 60 SD rats were subjected to 30% TBSA III degree scald injury, and randomly divided into scald group (with conventional fluid transfusion after scald) and ENA group (with intraperitoneal injection of 1 mg/kg Enalaprilat after scald). Normal control consisted of 6 rats. Plasma levels of cTnI and CK-MB were determined in all the groups at 1, 3, 6, 12, 24 post-scald hours (PSH) by enzyme linked immunosorbent assay. The pathological changes in myocardium were observed at the same time-points.

RESULTS(1) The serum level of cTnI and CK-MB in scald group were significantly higher than that of normal controls at each time-point (P < 0.01). The serum level of cTnI and CK-MB in ENA group were (1.32 +/- 0.12 microg/L to 2.47 +/- 0.22 microg/L) and (438 +/- 68 U/L to 5569 +/- 322 U/L), respectively, which were obviously lower than those in B group (6.42 +/- 0.96 microg/L to 15.10 +/- 3.69 microg/L) and (2556 +/- 74 U/L to 8047 +/- 574 U/L, P < 0.05 or P < 0.01) at different time-points. (2) Compared with normal controls, cloudy swelling, stromal blood vessel dilatation and congestion inflammatory cell infiltration were observed in scald group, but these pathological changes were less marked in ENA group.

CONCLUSIONSevere myocardial damage in rat occurred early after burns. Enalaprilat injection can markedly alleviate myocardial damage.

Animals ; Burns ; blood ; drug therapy ; pathology ; Creatine Kinase, MB Form ; blood ; Enalapril ; therapeutic use ; Myocytes, Cardiac ; metabolism ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Troponin I ; blood

OBJECTIVEDisturbances of the synthesis and breakdown of the extracellular matrix of arterial walls have emerged as key features of the atherosclerotic process. We observed the changes of circulating procollagen marker for type III collagen turnover rate, the N-terminal propeptide P III NP and vascular resistance in hypertensive patients treated with various antihypertensive regimens.

METHODA total of 130 light to moderate hypertensive patients were randomly assigned to receive enalapril (group B, n = 43), enalapril + spirolactone (20 mg/d, group A, n = 44) and anti-hypertensive drugs not directly affecting RAAS (calcium antagonist, beta-blocker, group C, n = 43) for 1 year. Target blood pressure is < 130/80 mm Hg.

RESULTSTarget blood pressure was reached in all treated patients and was similar among various groups. Under the same blood pressure controlling precondition, serum P III NP were similar at baseline among various groups and remained unchanged in group B [(3.4 +/- 0.3) microg/L vs. (3.7 +/- 0.3) microg/L, P > 0.05] and significantly decreased in group A [(2.3 +/- 0.2) microg/L vs. (3.8 +/- 0.2) microg/L, P < 0.05] while significantly increased in group C [(3.9 +/- 2.0) microg/L vs. (3.2 +/- 1.5) microg/L, P < 0.05]. Vascular resistance was similar among groups before therapy and all significantly decreased after 1 year antihypertensive therapy and the decrease was more significant in group A [(1064.3 +/- 158.6) dyn.s(-1).cm(-5)] than that in group B [(1200.8 +/- 298.7) dyn.s(-1).cm(-5)] and group C [(1205.1 +/- 206.4) dyn.s(-1).cm(-5)].

CONCLUSIONSpironolactone in conjunction with enalapril is a more favorable antihypertensive regimen in decreasing P III NP and improving vascular resistance than enalapril alone or antihypertensive drug regimens not directly affecting RAAS.

Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Biomarkers ; Enalapril ; therapeutic use ; Humans ; Hypertension ; drug therapy ; metabolism ; physiopathology ; Middle Aged ; Procollagen ; blood ; Spironolactone ; therapeutic use ; Vascular Resistance

OBJECTIVE: To explore the effect of p27 in the renal tubule on the process of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats, and to examine the expression changes of p27 after enalapril intervention and to interpret the anti-fibrotic mechanism. METHODS: Ninety rats were randomly divided into the sham-operated group (SOR), UUO group,and UUO+enalapril treatment group [enalapril: 10 mg/(kg.d)]. The rats of each group were respectively sacrificed on 7, 14, 21 days post-operatively. The renal pathological changes were dynamically observed by HE. The expression and dynamic changes of p27 were detected by immunohistochemistry. The level of p27 mRNA were detected by RT-PCR. RESULTS: The expression of p27 in renal tubular epithelial cells and p27 mRNA were strongly positive in the SOR group. With degree of interstitial fibrosis aggravating, the expression of p27 mRNA was gradually reducing. Enalapril could improve the expression of p27 on the 14th and 21st days after the UUO. CONCLUSION (1) This study supports a causative role of p27 in the formation of fibrosis of renal mesenchyme in rats with UUO. (2) The anti-fibrotic mechanism of enalapril is partly the improvement of p27 expression.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Cyclin-Dependent Kinase Inhibitor p27 ; biosynthesis ; genetics ; Enalapril ; pharmacology ; therapeutic use ; Female ; Kidney Tubules ; metabolism ; Nephrosclerosis ; drug therapy ; etiology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications