OJECTIVETo observe the effect of tianma gouteng decoction (TGD) on the endothelial function and the renal protein expression of spontaneously hypertensive rats, and to analyze its possible mechanism.

METHODSTotally 18 6-week-old SHR were randomly divided into 3 groups according to randomized block design, the SHR control group, the TGD group, and the captopril group, 6 in each group. Meanwhile, Wistar Kyoto (WKY) rats of the same age were recruited as a WKY control group. Rats in the TGD group were administered with TGD at the daily dose of 10. 260 g/kg. Rats in the captopril group were administered with captopril at the daily dose of 3. 375 g/kg. 2 mL/100 g distilled water was administered to rats in the SHR control group and the WKY control group. All medication was performed by gastrogavage once per day till rats were 24 weeks old. Changes of blood pressure were measured once per two weeks. The relaxation of the thoracic aorta and the superior mesenteric artery was determined by vascular ring in vitro to reflect the endothelial function. The total renal protein was separated by two-dimensional electrophoresis (2-DE). The significantly deviated protein was verified by Western blot.

RESULTS(1) Compared with the SHR control group, blood pressure was significantly lowered in rats (10 - 24 weeks old) of the captopril group (P <0.01, P <0.05). The hypotensive effect of TGD was obvious at the beginning of hypertension (10 -12 weeks) (P <0. 01). But along with the progression of hypertension, its hypotensive effect was not obvious (P>0. 05). (2) Compared with the SHR control group, the relaxation of the superior mesenteric artery was obviously improved in the TGD group (P <0. 05); the relaxation of the thoracic aorta and the superior mesenteric artery was obviously superior in the WKY control group (P <0. 01, P <0. 05). But there was no statistical difference in each relaxation index between the captopril group and the SHR control group (P >0. 05).(3) RESULTS: of 2-DE found 16 significantly differential renal protein, mainly involved nitric oxide (NO) system, oxidative stress, and cytoskeleton-related proteins. Results of Western blot showed that TGD could significantly improve expressions of Cu-Zn superoxide dismutase (SOD), N(G, N(G)-dimethylarginine dimethylaminohydrolase 2 (DDAH2), and pterin-4-alpha-carbinolamine dehydratase 1 (PCBD1) (P <0. 05).

CONCLUSIONGTD could protect the endothelial function of the superior mesenteric artery in SHR, and its intervention mechanism of hypertension induced early renal injury might be relevant to regulating the NO system and antioxidative stress.

Animals ; Blood Pressure ; Captopril ; Drugs, Chinese Herbal ; therapeutic use ; Hypertension ; drug therapy ; Kidney ; metabolism ; Oxidative Stress ; Proteins ; metabolism ; Proteomics ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Superoxide Dismutase ; metabolism

BACKGROUNDDiabetic retinopathy (DR) is one of the most common complications of diabetes. Angiotensin-converting enzyme inhibitor is thought to play an important role in preventing and treating retinal diseases in animal models of DR. The aim of the present study was to investigate the role of angiotensin-converting enzyme inhibitor (ACEI, captopril) in the treatment of patients with non-proliferative DR.

METHODSThree hundred and seventeen type 2 diabetic patients (88.05% of participants) without or with mild to moderate non-proliferative retinopathy were randomly divided into captopril group (n = 202) and placebo group (n = 115). All subjects received 24-month follow-up. General clinical examinations, including blood pressure and glycated hemoglobin, as well as comprehensive standardized ophthalmic examinations were performed. Color fundus photography and optical coherence tomography (OCT) were used to grade diabetic retinopathy and detect macular edema respectively.

RESULTSThe levels of blood pressure and glycated hemoglobin in the two groups of patients remained within the normal range during the entire follow-up and no significant difference was found between the initial and last visits, suggesting that ACEI drugs play a protective role on the DR patients independent of its anti-blood pressure role. DR classification showed that 169 eyes (83.66%) remained unchanged and the DR grade of 33 eyes (16.34%) increased in captopril group, while 84 eyes (73.04%) remained unchanged and the grade of 31 eyes (26.96%) increased in placebo group (P = 0.024). Captopril treatment improved macular edema in 55.45% eyes, which was significantly higher than the 37.39% improvement in placebo group (P = 0.002). No significant difference was found in the visual acuity between the two groups (P = 0.271).

CONCLUSIONCaptopril can improve or delay the development of DR and macular edema, which can be used in the early treatment of DR patients with type 2 diabetic mellitus.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Captopril ; therapeutic use ; Diabetic Retinopathy ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

OBJECTIVETo study the vascular endothelial function recovery and its mechanism of Banxia Baizhu Tianma Decoction (BBTD).

METHODS54 SH rats were randomly divided into three groups: the blank control group, BBTD group and Captopril treatment group. BBTD (at the daily dose of 4. 320 g crude drug/kg) and Captopril (at the daily dose of 3.375 g/kg) was administered from the 7th week to the 24th week. Another eighteen Wistar-Kyoto rats of the same ages were taken as the control. Medication was discontinued and effects were observed until the 32nd week. The blood pressure was determined by arterial carotis cannula. The concentration of serum NO2(-) and total anti-oxidation were determined by Griess and fluorescence recovery after photobleaching (FRAP). The acetylcholine (Ach)-dependent relaxation of superior mesenteric artery was detected using in vitro vascular ring. The mRNA expressions of IL-1, IL-6 and iNOS were detected by Real-time PCR at the 18th, 24th, and 32nd week.

RESULTSBBTD could significantly lower blood pressure of SHR and the concentration of serum NO2(-) at the 18th and 24th week (P<0.05). The total anti-oxidation of SH rats increased at the 18th week (P<0.01), and ACh-dependent relaxation of superior mesenteric artery increased at the 24th week. The mRNA expressions of IL-1 was markedly suppressed by BBTD at the 18th, 24th, and 32nd week (P<0.05), while IL-6 and iNOS mRNA expression were significantly lowered only at the 32nd week (P< 0.01). Captopril could significantly lower blood pressure of SHR at the 18th and 24th week (P<0.05). It significantly increased the total anti-oxidation of SH rats at the 18th week (P<0.01). However, it could not increase ACh-dependent relaxation of superior mesenteric artery and regulate the concentration of NO2(-) at the 18th, 24th, and 32nd week. The mRNA expression of iNOS was markedly suppressed by Captopril at the 24th and 32nd week, while mRNA expressions of IL-1 and IL-6 were significantly lower only at the 32nd week (P<0.01).

CONCLUSIONSBBTD showed similar effect in decreasing the blood pressure to captopril, but it showed better effect in improving the mesenteric endothelial dysfunction of SHR, which may be associated with its inhibition on NO and IL-1 expression, and improvement of the oxidative stress state.

Animals ; Captopril ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelium, Vascular ; drug effects ; metabolism ; Hypertension ; drug therapy ; metabolism ; physiopathology ; Interleukin-1 ; metabolism ; Interleukin-6 ; metabolism ; Male ; Mesenteric Arteries ; drug effects ; physiopathology ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

OBJECTIVETo compare the antifibrotic effect of oxymatrine and captopril in mice with chronic viral myocarditis (CVMC) and determine the possible antifibrotic mechanism of oxymatrine in CVMC.

METHODSNinety Balb/c mice were randomly divided into normal control group 1 (n = 10), normal control group 2(n = 10) and CVMC model group (n = 70). The mice in CVMC model group were infected with coxsackievirus B(3) (CVB(3)) on days 0, 14 and 28 to establish CVMC model. The volume of CVB(3) suspension was 0.20 ml, 0.25 ml and 0.30 ml, whose 50% tissue culture infection dose was 10(9) respectively. The mice in the normal control group 1 and 2 were given normal saline of volumes equal to those of viral suspension given to the model group at the same time points. Echocardiography and collagen specific picrosirius red staining were performed to evaluate the CVMC model on day 42 for the mice of the normal control group 1 and 8 mice of CVMC model group. The remaining mice in CVMC model group were randomly divided into CVMC control group, captopril group and oxymatrine group on day 42. From then on, the mice in captopril group and oxymatrine group were treated with captopril or oxymatrine at the dose of 100 mg/kg, by gavage once a day for 28 days, and meanwhile the mice in CVMC control group and the normal control group were given equal-volume normal saline by gastric gavage every day, for 28 days successively. All these mice were sacrificed on day 70. Heart tissue slices were stained with collagen specific picrosirius red and the collagen volume fraction (CVF) was calculated with image analysis software. The expressions of AngII and TGF-beta1 were determined by immunohistochemistry and Western blotting.

RESULTSCompared with normal group 1, the left ventricular end-diastolic internal diameters, left ventricular end-systolic internal diameters and heart rates were significantly increased in CVMC model group (P < 0.05, P < 0.01, P < 0.05, respectively), ejection fractions, fractional shortenings and peak velocity of aorta were all significantly decreased in CVMC model group (P < 0.01 for all comparisons), and CVF levels were significantly increased in CVMC group (P < 0.01) on day 42. Compared with normal control group 2, captopril group and oxymatrine group, CVF levels and the expressions of TGF-beta1 were significantly increased in CVMC control group (P < 0.01 for all comparisons) on day 70. The expressions of AngII in CVMC control group were higher than those in normal control group and captopril group (P < 0.01 for all comparisons), but there were no significant difference between oxymatrine group and CVMC control group (P > 0.05) on day 70.

CONCLUSIONOxymatrine can inhibit myocardial fibrosis in CVMC, and the mechanisms of its antifibrotic effects might be related with the down-regulation of TGF-beta1 expression.

Alkaloids ; therapeutic use ; Animals ; Antiviral Agents ; therapeutic use ; Captopril ; therapeutic use ; Chronic Disease ; Disease Models, Animal ; Down-Regulation ; Enterovirus B, Human ; Fibrosis ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; metabolism ; pathology ; virology ; Myocardium ; metabolism ; Quinolizines ; therapeutic use ; Transforming Growth Factor beta1 ; metabolism ; Virus Diseases ; pathology

OBJECTIVETo investigate the protective effects of captopril against lung injury in a rat model of severe acute pancreatitis (SAP).

METHODSSeventy-two male SD rats were randomized into sham-operated group (SO group), SAP group and captopril intervention group (CAP group). Serum amylase and myeloperoxidase (MPO) activity in the lung tissue were examined at 1, 6 and 12 h after the operation. TNF-α and AngII in the lung tissue were detected by ELISA, and the histopathological changes of the pancreas and lung were observed microscopically.

RESULTSThe MPO activity , which was similar between SAP group and CAP group at 1 h, were significantly lowered in CAP group at 6 and 12 h (P<0.05). Serum amylase level and the levels of TNF-α and AngII in the lung tissue homogenate were all reduced significantly in CAP group as compared to those in SAP group (P<0.01). The pathological injury of the lung was obviously lessened in CAP group in comparison with that in SAP group.

CONCLUSIONCaptopril can ameliorate SAP-induced lung injury in rats.

Amylases ; blood ; Angiotensin II ; metabolism ; Animals ; Captopril ; pharmacology ; therapeutic use ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Lung Injury ; etiology ; prevention & control ; Male ; Pancreatitis ; complications ; drug therapy ; Peroxidase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUNDS AND AIMS: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. Material and METHODS: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. Alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. RESULTS: Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (microgram/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA. CONCLUSIONS: Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats.
Actins/metabolism ; Angiotensin II Type 1 Receptor Blockers/administration & dosage/*therapeutic use ; Animals ; Bile Ducts/pathology/surgery ; Captopril/administration & dosage/*therapeutic use ; Fibrosis ; Hydroxyproline/metabolism ; Ligation ; Liver/drug effects/metabolism/pathology ; Liver Cirrhosis, Experimental/*drug therapy/etiology/metabolism ; Losartan/administration & dosage/*therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta/metabolism

OBJECTIVETo investigate the effect of Yiqi Huoxue Recipe (YHR) on the cardiac function and ultrastructure during the regression of myocardial hypertrophy induced by pressure overload in rats.

METHODSThe model of myocardial hypertrophy was established by abdominal aortic banding. Eighty male Wistar rats were divided into six groups, the normal control group I (n=20), the normal control group II (n=12), the hypertension model group I (n=12), the hypertension model group II (n=12), the YHR group (n=12) and the Captopril group (n=12). The observation was carried out in the normal control group I and the hypertension model group I after 4 weeks of modeling, and the other four groups were observed after 16 weeks of modeling (12 weeks of administration). The cardiac function was measured with a multichannel biological signal analysis system, and the myocardium ultrastructure was observed by a transmission electron microscope.

RESULTS(1) Compared with the normal control group I, the systolic blood pressure and cardiac coefficient (left ventricular weight/body weight) in the model I group was higher (P<0.05, P<0.01). (2) In the YHR group, cardiac coefficient and -dp/dt(max) were lower, left ventricular systolic pressure and +dp/dt(min) were higher when compared with the model group II and the Captopril group (P<0.05 or P<0.01). In the Captopril group, only cardiac coefficient was lower when compared with the mode group II (P<0.05). (3) Compared with the normal control group II, +dp/dt(max) was higher (P<0.01) -dp/dt(max) and isovolumetric contraction time (ICT) was lower (P<0.05, P<0.01) in both the YHR group and the Captopril group. (4) Results of the myocardium ultrastructure showed edema under myocardium plasmalemma, enlarged sarcoplasmic reticulum and T tube, and significantly enlarged intercalated disc of the cardiac muscle in the model groups. In the Captopril group, the extension of sarcoplasmic reticulum and T tube as well as the pathological changes of intercalated disc were lighter, with slight edema under the myocardium plasmalemma. In the YHR group, the expansion of the sarcoplasmic reticulum was less than in the Captopril group, part of the pathological changes of intercalated discs was slightly more severe than that in the Captopril group, the dissolution of nuclear chromatin was not found, which was similar to that of the Captopril group, and no injury of the nucleus was found, either.

CONCLUSIONYHR could reverse myocardial hypertrophy in rats with abdominal aortic banding and improve the systolic and diastolic function of the left ventricle. The ultrastructure of the myocardium such as arcoplasmic reticulum, intercalated disc, and cell nucleus in abdominal aortic banding rats could be partly reversed by the recipe.

Animals ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Captopril ; therapeutic use ; Cardiomegaly ; drug therapy ; etiology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart ; drug effects ; physiology ; Male ; Myocardium ; ultrastructure ; Phytotherapy ; Pressure ; Rats ; Rats, Wistar ; Remission Induction ; Ventricular Remodeling ; drug effects

OBJECTIVEThis study examined the protein and mRNA contents of angiotesin converting enzyme (ACE), angiotensin II (Ang II) and type I collagen and the changes of lung histomorphology in neonatal rats with hyperoxia-induced chronic lung disease (CLD) and investigated the protection of captopril against CLD and the possible mechanism.

METHODSA total of 240 term neonatal Wistar rats were randomly assigned into air, model, normal saline and captopril-treated groups (n=60 each). The air group was exposed to room air (FiO2=0.21) immediately after birth. The other three groups were exposed to hyperoxia (FiO2=0.9) for 21 days to induce lung injury. The captopril-treated group received captopril daily (30 mg/kg) by intragastric administration between the 7th and 21st days of hyperoxia exposure. The normal saline group was administrated with normal saline instead. At each time interval of 1, 3, 7, 14 and 21 days after experiment, six rats of each group were randomly chosen and sacrificed. The protein and mRNA levels of ACE, Ang II and type I collagen were measured by enzyme-linked immunosorbentassay, radio-immunity technique and RT-PCR. The changes of lung histomorphology were observed under a light microscope.

RESULTSThe protein and mRNA expressions of ACE, Ang II and type I collagen increased significantly in the model and normal saline groups on the 14th and peaked on the 21st days of exposure compared with those of the air group (P < 0.05 or 0.01). Captopril treatment reduced significantly the protein and mRNA expressions of ACE, Ang II and type I collagen compared the model and normal saline groups on the 14th and 21st days, although the values were significantly higher than the air group (P < 0.05 ). The histopathologic examination demonstrated broadened lung interstitium and reduced alveolar quantity and lung fibrosis was developed in the model and normal saline groups on the 14th day of exposure. Captopril treatment obviously alleviated the changes of lung histomorphology.

CONCLUSIONSCaptopril can inhibit the protein and mRNA expressions of ACE, Ang II and type I collagen and alleviate lung fibrosis in neonatal rats with hyperoxia-induced lung injury/CLD. This may contribute to one of the possible mechanisms underlying the protective effects of captopril against lung injury/CLD.

Animals ; Animals, Newborn ; Body Weight ; drug effects ; Captopril ; therapeutic use ; Chronic Disease ; Collagen Type I ; analysis ; Hyperoxia ; complications ; Lung ; metabolism ; pathology ; Lung Diseases ; prevention & control ; Peptidyl-Dipeptidase A ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

Animals ; Arrhythmias, Cardiac ; etiology ; therapy ; Captopril ; therapeutic use ; Disease Models, Animal ; Electric Stimulation Therapy ; methods ; Myocardial Ischemia ; physiopathology ; therapy ; Rabbits ; Ventricular Fibrillation

OBJECTIVETo observe the effects of Xinshuai Mistura (XM) on plasma angiotensin II (Ang II), atrial natriuretic peptide (ANP) and N terminal pro- brain natriuretic peptide (Nt-proBNP) in patients with heart failure (HF).

METHODSFifty-nine patients with HF (NYHA class II-IV) were randomly divided into two groups, the treated group treated with XM and the control group with Wuling Pulvis (WP), both on the base of captopril treatment. The treatment course was two weeks. Plasma levels of Ang II , ANP and Nt-proBNP were observed.

RESULTSThe plasma levels of Ang I, ANP and Nt-proBNP showed an ascending tendency along with the increasing in severity of HF(P < 0.01), and significantly decreased after treatment in the treated group (P < 0.01), but with no remarkable difference as compared with those in the control group (P > 0.05).

CONCLUSIONXM had definite therapeutic effects on excessive neuroendocrine activation in HF patients.

Adult ; Aged ; Angiotensin II ; blood ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Atrial Natriuretic Factor ; blood ; Captopril ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Failure ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Phytotherapy ; Single-Blind Method ; Treatment Outcome