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

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

OBJECTIVE: To investigate the effect of pretreatment with captopril on myocardium ischemia-reperfusion injury in atherosclerotic rabbits. METHODS: Thirty-two New Zealand white rabbits were assigned randomly to the normally feed group, cholesterol-feed (CF) group, and cholesterol food plus captopril group (cap-feed group), which were fed for 10 weeks. We examined the changes in the size of the infarct and changes in the myocardium ultrastructure resulting from coronary ischemia/reperfusion. Levels of endothelin (ET) and nitic oxide (NO) were measured in the different experiment stages. RESULTS: The ET levels significantly increased and the content of NO significantly decreased in the CF group compared with those of the cap-feed group. The ultrastructure of myocardium cell was slightly destroyed and the infarct size was significantly smaller in the cap-feed group than the normally feed rabbits and CF rabbits. CONCLUSION The long-term captopril treatment can lighten the severity of myocardial injury produced by coronary ischemia/reperfusion.
Animals ; Captopril ; pharmacology ; therapeutic use ; Endothelins ; blood ; Male ; Myocardial Infarction ; blood ; drug therapy ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; ultrastructure ; Nitric Oxide ; blood ; Rabbits ; Random Allocation

OBJECTIVETo investigate the role of angiotensin converting enzyme inhibitor (ACEI) in the treatment of acute respiratory distress syndrome (ARDS).

METHODSChanges in physiological and biochemical indexes, and circulating endothelial cells (CEC) were observed in rats of oleic acid-induced ARDS with ACEI-Captopril (Cap) therapy and controls, respectively.

RESULTSUnder the normal systemic blood pressure, Captopril therapy showed good effect on ARDS in rats. Two hours after administration of Captopril, their pulmonary arterial pressure reduced to (14.43 +/- 1.51) mm Hg (1 mm Hg = 0.133 kPa), approximating to normal level, from (23.50 +/- 5.79) mm Hg. The number of CEC, which reflected injuries in pulmonary capillaries, decreased to (4.25 +/- 0.20)/0.9 micro l from (6.88 +/- 1.90)/0.9 micro l. Value of oxygen pressure in arterial blood (PaO(2)) increased to (70.48 +/- 9.54) mm Hg from (35.08 +/- 4.59) mm Hg. In the mean time, ratio of wet to dry lung weight was returned to nearly normal. So, it indicated that high-dose of oleic acid could only induce mild lung injury, and the development of ARDS was obviously inhibited by ACEI.

CONCLUSIONSACEI may effectively depress pulmonary arterial hypertension, block the development of ARDS, and have certain good protective effect on pulmonary capillary endothelia.

Acute Disease ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Animals ; Captopril ; therapeutic use ; Disease Models, Animal ; Endothelium, Vascular ; drug effects ; physiopathology ; Hypertension, Pulmonary ; complications ; drug therapy ; Male ; Oleic Acid ; Rats ; Rats, Wistar ; Respiratory Distress Syndrome, Adult ; chemically induced ; etiology ; prevention & control

OBJECTIVETo investigate the changes and the effects of captopril on the renal blood flow and microvascular perfusion in dogs with acute cardiac insufficiency.

METHODSAcute cardial insufficiency was induced by combining occlusion of the left anterior descending artery with right ventricular pacing in 12 mongrel dogs. The ascending aorta and left kidney were dissected and ultrasonic flow probes were placed on ascending aorta and renal artery to monitor cardiac output (CO) and renal blood flow (RBF). Contrast-enhanced ultrasound of the kidney was performed as CO was reduced to 25% (LCO25%) and 50% (LCO50%) from the basic measurement and microvascular flow velocity (beta), microvascular volume (A) and microvascular blood flow (renal cortex) were observed. After CO reduced to 50%, captopril 1 mg/kg and 2 mg/kg were injected successively and contrast-enhanced ultrasound of the kidney were performed again before and after injection.

RESULTSAt baseline, CO, RBF, CXbeta (beta of renal cortex), A and A x beta were (1.46 +/- 0.16) ml/min, (107.5 +/- 35.7) ml/min, 1.39 +/- 0.14, 120.3 +/- 14.8 and 167.4 +/- 25.0, respectively. After the LCO25% was reached, RAF, CXbeta, A and A x beta decreased to (72.50 +/- 32.4) ml/min, 0.87 +/- 0.082, 117.6 +/- 13.1, and 102.6 +/- 15.5, respectively. The corresponding values after the LCO50% was reached were (44.1 +/- 17.2) ml/min, 0.61 +/- 0.039, 106.9 +/- 12.0, and 64.7 +/- 8.83, respectively. It is suggested that the volume of the renal microvasculature remained stable until the LCO50% was reached. When captopril 1 mg/kg and 2 mg/kg were injected successively at LCO50%, MAP decreased from (85.4 +/- 7.8) mm Hg to (78.7 +/- 7.3) mm Hg and to (69.1 +/- 6.3) mm Hg (P < 0.05), respectively, while CO increased from 0.73 +/- 0.084 to 0.83 +/- 0.065 and to 0.9 +/- 0.054 (P < 0.05), respectively. RBF increased from (44.1 +/- 17.2) ml/min to 60.3 +/- 17.8 and to 79.4 +/- 17.8 (P < 0.05), respectively. After captopril 1 mg/kg and 2 mg/kg were injected, the increased flow ratios with CO were 0.15 +/- 0.084 and 0.31 +/- 0.011, respectively, and with RBF were 0.29 +/- 089 and 0.522 +/- 0.040, respectively. The increased renal blood flow ratio was higher than that of CO after captopril was used. The corresponding increases were from 0.61 +/- 0.039 to 0.75 +/- 0.020 and to 0.86 +/- 0.027 for CX beta, from 106.9 +/- 11.9 to 115.4 +/- 11.1 and to 116.6 +/- 8.9 for A, from 64.7 +/- 8.83 to 87.0 +/- 8.6 and to 100.6 +/- 8.9 for A x beta, respectively.

CONCLUSIONThe renal microvasculature plays a role by keeping its volume stable in the protection against renal ischemia when acute cardiac output decreases slightly. The role of captopril to improve renal microvascular perfusion is independent of increased total cardiac output or increased systemic blood pressure.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Captopril ; pharmacology ; therapeutic use ; Cardiac Output, Low ; complications ; drug therapy ; physiopathology ; Dogs ; Female ; Kidney ; blood supply ; diagnostic imaging ; Male ; Perfusion ; Renal Circulation ; drug effects ; Ultrasonography

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 evaluate the efficacy of Breviscapine on essential hypertension (EH) patients complicated with micro-albuminuria of renal impairment.

METHODSSeventy-six EH patients were randomly assigned to the control group and the treated group, the former was given amlodipine, captopril/uropidil and the latter was given in addition Breviscapine intravenously dripped for 2 treatment courses. The indexes of serum creatinine (Cr), blood urea nitrogen (BUN), blood and urinary beta(2)-microglobulin (beta(2)-MG), and quantitative determination of 24 hrs urinary protein were evaluated before and after treatment.

RESULTSIn the control group, compared with before treatment, the quantitative determination of 24 hrs urinary protein got reduced significantly (P < 0.05), while in the treated group, both urinary beta(2)-MG and quantitative determination of 24 hrs urinary protein got lowered significantly (P < 0.05 and P < 0.01). But after treatment, compared with the control group, urinary beta(2)-MG and quantitative determination of 24 hrs urinary protein in the treated group were obviously reduced (P < 0.05).

CONCLUSIONBesides lowering blood pressure effectively, Breviscapine could improve the renal function significantly and reduce the urinary micro-albuminuria, hence showing promising effect on renal protection.

Adult ; Aged ; Albuminuria ; etiology ; physiopathology ; Amlodipine ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Captopril ; therapeutic use ; Drug Therapy, Combination ; Female ; Flavonoids ; administration & dosage ; adverse effects ; therapeutic use ; Flushing ; chemically induced ; Humans ; Hypertension ; complications ; drug therapy ; physiopathology ; Injections, Intravenous ; Kidney Diseases ; etiology ; urine ; Male ; Middle Aged ; Proteinuria ; etiology ; physiopathology ; beta 2-Microglobulin ; urine

OBJECTIVETo examine the negative regulation role of PTEN in isoproterenol-induced cardiac hypertrophy by testing the expression of PTEN mRNA and protein and to explore the effects of captopril (Cap) on PTEN expression.

METHODSTwenty four rats were randomly divided into three groups: control group, ISO group, and ISO+Cap group. The following parameters were examined:body weight (BW), heart weight (HW), left ventricular weight (LVW), left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP) and +/- dp/dt(max). The ratio of HW/BW and LVW/BW was calculated. PTEN mRNA and protein were tested by RT-PCR and Western blot, respectively.

RESULTS(1) Compared with the control group, the ratio of HW/BW and LVW/BW, LVEDP and LVESP were all increased in ISO group and ISO+Cap group (P < 0.05), but +/- dp/dt(max) was decreased (P < 0.05); (2) compared with the ISO group, the ratio of HW/BW and LVW/BW, LVEDP, LVESP were all decreased in ISO+Cap group (P < 0.05), but +/- dp/dt(max) was increased (P < 0.05); (3) compared with the control group, PTEN mRNA and protein were up-regulated in ISO group and ISO+Cap group; (4) compared with the ISO group, PTEN mRNA and protein were up-regulated in ISO+Cap group.

CONCLUSIONSPTEN mRNA and protein are up-regulated in isoproterenol-induced cardiac hypertrophy. Captopril can up-regulate PTEN expression in cardiac hypertrophy. There is a negative regulative mechanism in cardiac hypertrophy process, in which PTEN is probably an endogenous negative regulator of cardiac hypertrophy.

Animals ; Captopril ; therapeutic use ; Cardiomegaly ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Gene Expression Regulation ; Isoproterenol ; adverse effects ; Myocardium ; metabolism ; ultrastructure ; PTEN Phosphohydrolase ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar

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

The effect of captopril on proteinuria was evaluated in twenty patients with various glomerular diseases excreting heavy proteinuria (> 3.0 g/day). Captopril in a daily dose of 37.5 mg was administered orally three times a day to all patients and they were followed for eight weeks. Twenty-four hour urinary excretion of protein, creatinine, sodium, selective protein index (SPI), and blood chemistry including serum electrolytes were measured every two weeks. Twenty-four hour urinary protein excretion per gram creatinine started to fall within two weeks of captopril administration and became nearly stable after four weeks of therapy (p< 0.05). Mean 24-hour urinary protein excretion decreased significantly from a pretreatment value of 9.0 +/- 6.0 gm/gm of cr. to 4.4 +/- 3.5 gm/gm of cr. after eight weeks of captopril treatment. The serum albumin level increased progressively at six and eight weeks after the captopril treatment period and was significantly higher than the pretreatment value (p< 0.05). The decrease in proteinuria did not coincide with a fall in blood pressure or any changes in creatinine clearance. We conclude that captopril does have a significant antiproteinuric effect in patients excreting heavy proteinuria with various glomerular diseases. However, the long term therapeutic efficacy and any renal protective effect of this drug remain to be proven.
Adult ; Aged ; Blood Pressure/drug effects ; Captopril/*therapeutic use ; Female ; Glomerulonephritis/*drug therapy ; Glomerulonephritis, IGA/*drug therapy ; Glomerulonephritis, Membranous/*drug therapy ; Human ; Male ; Middle Age ; Proteinuria/*drug therapy ; Sodium/urine ; Support, Non-U.S. Gov't