Animals ; Cardiomyopathy, Hypertrophic ; drug therapy ; physiopathology ; Disease Models, Animal ; Enalapril ; pharmacology ; therapeutic use ; Rabbits ; Ventricular Remodeling

OBJECTIVETo compare the effects of high, middle and low doses of enalapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, especially evaluating the efficacy of low dose enalapril.

METHODSAMI was induced by ligating the left coronary artery in 149 female SD rats. 48 hours after the procedure, the 97 surviving rats were randomized to one of the following four groups: (1) AMI controls (n = 24), (2) high-dose (10 mg x kg(-1) x d(-1), n = 25), (3) middle-dose (1 mg x kg(-1) x d(-1), n = 23), and (4) low-dose (0.1 mg x kg(-1) x d(-1), n = 25) enalapril groups. In addition, sham-operated (n = 13) and normal rats (n = 10) were randomly selected to serve as non-infarction controls. Enalapril was delivered by direct gastric gavage. After 4 weeks of therapy, hemodynamic studies were performed, then the rat hearts were fixed with 10% formalin and pathology analysis was performed. Exclusive of the dead rats and those with MI size < 35% or > 55%, complete experimental data were obtained from 67 rats, which were comprised of (1) AMI controls (n = 13), (2) high-dose enalapril (n = 13), (3) middle-dose enalapril (n = 12), (4) low-dose enalapril (n = 12), (5) sham-operated (n = 8) and (6) normal (n = 9) groups.

RESULTSThere were no significant differences among the four AMI groups in infarction size (all P > 0.05). Compared with the sham-operated group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), absolute and relative weight (LVAW, LVRW) in AMI group were all significantly increased (all P < 0.001), while maximum LV pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were all significantly reduced in the AMI control group (P < 0.01 - 0.001), indicating LVRM occurred and LV systolic and diastolic functions were impaired. Compared with the AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased in the three enalapril groups (control P < 0.001), with the reduction of LVEDP, LVV and LVAW being more significant in high-dose than in low-dose enalapril groups (all P < 0.05), and the +/- dp/dt/LVSP were significantly increased only in the high and middle-dose enalapril groups (P < 0.01).

CONCLUSIONSHigh, middle and low doses of enalapril were all effective in preventing LVRM after AMI in the rat, with low dose enalapril being effective and high dose superior. As for LV functional improvement, only high and middle-dose enalapril were effective.

Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; pharmacology ; Animals ; Dose-Response Relationship, Drug ; Enalapril ; administration & dosage ; pharmacology ; Female ; Myocardial Infarction ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Ventricular Remodeling ; drug effects

OBJECTIVETo observe the changes in the myocardial ultrastructure of diabetic rats and the effect of enalapril treatment.

METHODSMale Wistar rats were divided into 3 groups, namely the control group, diabetic group and enalapril intervention group. Diabetes was induced with peritoneal injection of streptozotocin in the latter 2 groups, and in enalapril group, the rats were treated with enalapril at the daily oral dose of 2 mg/kg for 1, 3 and 5 months after streptozotocin injection. Histological analysis of the left ventricular tissue was performed with transmission electron microscope 1, 3, and 5 months after establishment of diabetes.

RESULTSOnset of myocardial damages was observed 1 month after the development of diabetes in the rats with gradual time-dependent exacerbation. Enalapril treatment could partially reverse the myocardial destruction in the diabetic rats.

CONCLUSIONEnalapril intervention may improve the ultrastructural pathology of the myocardium in diabetic rats, which is suggestive of the action mechanisms of angiotensin-converting enzyme inhibitors in myocardium preservation.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Diabetes Mellitus, Experimental ; drug therapy ; pathology ; Enalapril ; pharmacology ; Male ; Myocardium ; ultrastructure ; Rats ; Rats, Wistar ; Streptozocin

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.
Animals ; Antihypertensive Agents/*pharmacology ; Atrophy ; Benzimidazoles/pharmacology ; Benzoates/pharmacology ; Bone Density/*drug effects ; Enalapril/pharmacology ; Female ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; Propranolol/pharmacology ; Thiazides/pharmacology ; Tibia/radiography ; Tomography, X-Ray Computed ; Uterus/anatomy & histology/pathology

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.
Animals ; Antihypertensive Agents/*pharmacology ; Atrophy ; Benzimidazoles/pharmacology ; Benzoates/pharmacology ; Bone Density/*drug effects ; Enalapril/pharmacology ; Female ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; Propranolol/pharmacology ; Thiazides/pharmacology ; Tibia/radiography ; Tomography, X-Ray Computed ; Uterus/anatomy & histology/pathology

The present study investigated the interaction between sodium loading and enalapril on renin synthesis and secretion in hydronephrotic mice. Four different experimental groups (n=10 each) were used: sham-operated animals with normal diet (control group); sodium loading (SL group); enalapril treatment with normal diet (E group), and sodium loading combined with enalapril treatment (SL+E group). The hydronephrotic left kidney was induced by unilateral ureteral ligation in mice in the latter three groups. Plasma renin concentration (PRC) in the aorta, both the left and right renal veins, tissue renin concentration (TRC) and renin mRNA levels in the kidneys were examined under different procedures. In hydronephrotic mice treated with sodium loading, PRC in the left and right renal veins was lower than that in control mice (P<0.05), and TRC and renin mRNA levels in the hydronephrotic kidney were also suppressed (P<0.05). In hydronephrotic mice treated with enalapril, there were significant increases in PRC, TRC and renin mRNA levels in the hydronephrotic and right kidneys compared to the normal control (P<0.01). In hydronephrotic animals treated with sodium loading and enalapril, the increasing response was attenuated, and PRC in the hydronephrotic vein was similar to the level in the aorta. There was an interaction between sodium loading and enalapril on renin-angiotensin system (RAS) in both hydronephrotic and normal kidneys. The mechanism in control of renin synthesis is independent of the macula densa, but the latter is critical in the control of renin secretion.
Animals ; Aorta ; metabolism ; Enalapril ; pharmacology ; Hydronephrosis ; metabolism ; Kidney ; physiopathology ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; metabolism ; Renin ; metabolism ; Renin-Angiotensin System ; drug effects ; Sodium ; metabolism

OBJECTIVESTo compare the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in the rat.

METHODSAMI model was induced in female SD rats by ligating left coronary artery. Forty-eight hours after the procedure, 83 surviving rats were randomized into one of the following 4 groups : 1) AMI control group (n = 19), 2) losartan group (n = 22, 3 mg x kg(-1) x d(-1)), 3) enalapril group (n = 20, 1 mg x kg(-1) x d(-1)), 4) losartan-enalapril combinative group (n = 22, 3 and 1 mg x kg(-1) x d(-1) respectively). 5) Sham-operated group (n = 10) and 6) normal rats group (n = 10) were selected randomly to serve as non-infarction controls. Losartan and enalapril were delivered by direct gastric gavage. After 4 weeks of medical therapy, hemodynamic studies were performed in each group, then the rat hearts were fixed with 10% formalin and pathologic analysis on them was performed. Complete experimental data was obtained in 56 rats, comprising 1) AMI controls (n = 11), 2) losartan group (n = 10), 3) enalapril group (n = 10), 4) the combination of losartan and enalapril group (n = 11), 5) sham-operated group (n = 6) and 6) normal controls (n = 8).

RESULTSThere were no significant differences among the 4 AMI groups in MI size (41.7% to approximately 43.4%, all P > 0.05). Compared with sham group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), long and short axis length (L and D), as well as LV absolute and relative weight (LVAW and LVRW) in AMI group were all significantly increased (P < 0.05 to approximately 0.001); whereas the maximum left ventricular pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were significantly reduced (all P < 0.001), indicating LVRM occurred and LV systolic and diastolic function impaired after AMI. Compared with AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased (P < 0.05 to approximately 0.001); while +/- dp/dt/LVSP were significantly enhanced in all 3 treatment groups (P < 0.05 to approximately 0.001) except -dp/dt/LVSP in losartan group (P > 0.05). There were no significant differences in the above indices among the 3 treatment groups (all P > 0.05).

CONCLUSIONBoth losartan and enalapril can prevent from LVRM after AMI in the rat and improve LV function with equivalent effects. There seems no additive effect when the 2 drugs are used in combination.

Animals ; Antihypertensive Agents ; pharmacology ; Drug Synergism ; Enalapril ; pharmacology ; Female ; Losartan ; pharmacology ; Myocardial Infarction ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ventricular Function, Left ; drug effects ; Ventricular Remodeling ; drug effects

This study sought to assess the effects of Quercetin and Enalapril on urinary protein excretion and amount of platelet-derived growth factor-B (PDGF-B) and vascular endothelial growth factor-1 (VEGF-1) in renal tissue of diabetic rats. 29 streptozotocin-induced diabetic rats were divided into 3 groups, diabetic control group (group D, n=12); Enalapril group (group E, n=10); Quercetin group (group Q, n=7). In addition, there was one normal control group (group N, n = 5). The urinary protein excretion of 24 hours was measured at 4, 8, 12 weeks. All rats were sacrificed at 12 weeks. The amounts of PDGF-B and VEGF-1 in renal tissue were measured by immunohistochemical techniques. The 24-h levels of urinary protein excretion of D,Q and E groups were higher than that of N group; the level of Q, E groups were lower than that of D group; there was no difference between Q and E group. The expression levels of PDGF-B and VEGF-1 in renal tissue of D, Q, and E groups were significantly higher than that of N group the levels of Q and E groups were significantly lower than that of D group, no difference was found between Q and E group. The protective role of Quercetin and Enalapril in lowering urinary protein excretion may be related to the decreased amounts of PDGF-B and VEGF-1 in renal tissue.
Animals ; Diabetes Mellitus, Experimental ; metabolism ; Enalapril ; pharmacology ; Kidney ; metabolism ; Male ; Proteinuria ; metabolism ; Proto-Oncogene Proteins c-sis ; metabolism ; Quercetin ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: To investigate the effect Pinggan Qianyang recipe on expression of Tpx, HSP27 and ANXA1 in the hypothalamus of spontaneously hypertensive rats (SHRs) with the hyperactivity of liver-YANG syndrome. METHODS: A total of 30 SHRs were subjected to administration of Aconiti Praeparatae Decoction to establish the model of SHR with liver-YANG hyperactivity first, then they were randomly divided into three groups: the control group, the model group and the treatment group (n=10 per group). A total of 10 SD rats were served as the normal group. The rats in control group and treatment group were given Enalapril plus Pinggan Qianyang recipe for four weeks. The change of behavior and blood pressure of rats were monitored. RT-PCR and Western-blot were performed to detect the expression of Tpx II, HSP27 and ANXA1 mRNA and protein in the hypothalamus, respectively. RESULTS: Compared with the normal SD rats, the heart rate, blood pressure and grade of irritability were significantly increased while rotation endurance time was dramatically reduced in the SHR model with liver-YANG hyperactivity (P<0.01), these changes were reversed by the application of Enalapril plus Pinggan Qianyang recipe. Compared with the normal SD rats, the protein and mRNA expression of Tpx II and ANXA1 in the model group were significantly upregulated (P<0.01) while the HSP27 was significantly downregulated (P<0.01). Compared with the model group, the protein and mRNA expression of Tpx II and ANXA1 in the control group or treatment group were significantly decreased (P<0.05 or P<0.01) while HSP27 was significantly increased (P<0.05 or P<0.01). Compared with the control group, the expression of Tpx II and ANXA1 protein in treatment group were significantly reduced (P<0.05 or P<0.01). CONCLUSION Pinggan Qianyang recipe can improve the blood pressure and behavior in SHRs with hyperactivity of Liver-YANG syndrome, which might be related to the regulation of Tpx, HSP27 and ANXA1 expression in hypothalamuses.
Animals ; Annexin A1 ; metabolism ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Enalapril ; pharmacology ; HSP27 Heat-Shock Proteins ; metabolism ; Hypothalamus ; drug effects ; metabolism ; Liver ; physiopathology ; Rats ; Rats, Inbred SHR

OBJECTIVE: To investigate the expression of P21 in renal interstitial fibrosis rats and the effect of enalapril on it. METHODS: Sprague Dawley rats were randomly divided into 3 groups: a sham operation group,a unilateral urethral obstruction group, and an enalapril treatment group. The expression of P21 in renal tubular epithelial cells on the process was detected by immunohistochemistry at different time spots (7, 14, 21 d after UUO, sham-surgery or enalapril treatment). The expression of p21 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Seven days after the surgery, significant differences were found in P21 expression between UUO and SOR renal tubular cells. With degree of interstitial fibrosis aggravating, P21 expression increased. Enalapril can inhibit its expression. CONCLUSION In the kidney of UUO rats, P21 expression increased and enalapril possessed significant inhibitory effects on the procedure. P21 may participate in the pathogenesis of renal tubule-interstitial fibrosis.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Enalapril ; pharmacology ; therapeutic use ; Kidney Tubules ; metabolism ; Male ; Nephrosclerosis ; drug therapy ; metabolism ; Proto-Oncogene Proteins p21(ras) ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications