OBJECTIVETo observe the effects of Danhong Injection (丹红注射液) and its main components, including daiclzein and hydroxysafflor yellow A (HSYA), on the anticoagulation, fibrinolysis, anti-apoptosis in hypoxia model of vein endothelial cells (VECs).

METHODSVECs were prepared and were put in a hypoxia environment, which consisted of mixed gas of 95% N and 5% CO mixed gas, when reached confluent culture. Five groups used different treatments, including normal control group, hypoxia group, daiclzein group, HSYA group and Danhong Injection group. The VECs were identified by fluorescence double labeling methods. The morphology was observed by a phase contrast microscopy. The effects of Danhong Injection, daiclzein and HSYA on 6 keto prostaglandin F1α (6-keto-PGF1α) level was measured by the method of radioimmunoassay (RIA). Superoxide dismutase (SOD) activity was tested by water soluble tetrazolium salt. The content of malondialdehyde (MDA) was measured by thiobarbituric acid. The activities of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were measured by the method of chromogenic substrate. The contents of endothelin (ET) and nitric oxide (NO) were detected by non-equilibrium RIA and enzymelinked immunosorbent assay. Cells apoptosis rate was determined by flow cytometry.

RESULTSCompared with the normal control group, the floating cells number, PAI activity, ET and MDA contents, and cells apoptosis rate in the culture solution of hypoxia group were all significantly increased, whereas the 6-keto-PGF1α and NO contents, and t-PA and SOD activities were decreased significantly (P<0.01). Compared with the hypoxia group, Danhong Injection markedly increased the 6-keto-PGF1α content and SOD activity, regulated PAI and t-PA activities, ET and NO contents, and decreased MDA content and cells apoptosis rate (P<0.05 or P<0.01).

CONCLUSIONSDanhong Injection and its main components played an important role in protecting primary VECs from hypoxic damage by regulating the secretion and vasomotor function of VECs. The function of Danhong Injection was most remarkable.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Apoptosis ; drug effects ; Blood Coagulation ; drug effects ; Cell Count ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Endothelins ; metabolism ; Factor VIII ; metabolism ; Fibrinolysis ; drug effects ; Fluorescent Antibody Technique ; Humans ; Infant, Newborn ; Injections ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Plasminogen Inactivators ; metabolism ; Rabbits ; Superoxide Dismutase ; metabolism ; Tissue Plasminogen Activator ; metabolism ; Umbilical Veins ; cytology

OBJECTIVETo investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension.

METHODSA randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment.

RESULTSAfter treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05).

CONCLUSIONIn patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.

Aged ; Atorvastatin Calcium ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Endothelins ; blood ; Exercise Tolerance ; drug effects ; Female ; Heart Failure ; complications ; drug therapy ; physiopathology ; Heptanoic Acids ; pharmacology ; Humans ; Hypertension ; complications ; drug therapy ; physiopathology ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Prospective Studies ; Pyrroles ; pharmacology

Angiotensin II ; metabolism ; Cells, Cultured ; Endothelial Cells ; drug effects ; secretion ; Endothelins ; secretion ; Humans ; Polyphenols ; pharmacology ; Propanolamines ; pharmacology ; Tea ; chemistry ; Weightlessness Simulation

The aim of this study is to study the effect of calcium dobesilate on streptozotocin (STZ)-induced early diabetic nephrophathy (DN) in rats. All male Wistar rats were randomly divided into six groups: normal group; DN blank group; calcium dobesilate 75, 150, and 300 mg x kg(-1) groups and perindopril 0.4 mg x kg(-1) group. Blood glucose and the 24 h urinary albumin were measured dynamically during the experiment, after 8 weeks administration, the level of glycosylated hemoglobin (HbA1c) was determined, the expressions of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloprotein-9 (MMP-9) in cortex of kidney were examined with immunohistochemical staining. The endothelin (ET) in plasma and kidney cortex was measured with radioimmunoassay, renal pathomorphism was observed with light and electron microscopes. Calcium dobesilate could decrease the 24 h urinary albumin and ET in plasma and kidney cortex, down-regulate the expression of PAI-1, and up-regulate MMP-9 in kidney. These findings suggested that calcium dobesilate could protect blood vessel endothelium, inhibit kidney fibrous degeneration, ameliorate renal pathological damage, and protect kidney function in many ways.
Albuminuria ; Animals ; Blood Glucose ; metabolism ; Calcium Dobesilate ; pharmacology ; Diabetes Mellitus, Experimental ; blood ; metabolism ; pathology ; Diabetic Nephropathies ; blood ; metabolism ; pathology ; Endothelins ; blood ; metabolism ; Glycated Hemoglobin A ; metabolism ; Hemostatics ; pharmacology ; Kidney Cortex ; metabolism ; ultrastructure ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Plasminogen Activator Inhibitor 1 ; metabolism ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the effect of octacostyl alcohol preparation on the motor function, blood free radical metabolism and cardiac endocrine function of rats.

METHODSA rat model of exercise fatigue was used for this study. The rats were made to perform continuous exhaustive exercise, and the total exercise time of the rats till exhaustion was recorded followed by examination of the serum superoxide dismutase (SOD), malonaldehyde (MDA), plasma endothelin (ET), calcitonin gene-related peptide (CGRP), and atrial natriuretic peptide (ANP).

RESULTSCompared with rats without interventions for exercise fatigue, the rats receiving octacostyl alcohol preparation had significant prolonged exercise time till exhaustion (P<0.05), with also significantly enhanced serum SOD activity (P<0.05), significantly decreased MDA level and plasma ET (P<0.05) and increased CGRP and ANP levels (P<0.05). Octacostyl alcohol preparation produced more favorable effect on all the indices measured than pyruvic acid-creatine (P<0.05).

CONCLUSIONThe octacostyl alcohol preparation can promote the motor function, increases blood antioxidase activity, suppressed lipid peroxidation in rats engaged in exhaustive exercise. The preparation also produces favorable effect on cardiac endocrine function for heart protection during exercise.

Animals ; Atrial Natriuretic Factor ; blood ; Calcitonin Gene-Related Peptide ; blood ; Drugs, Chinese Herbal ; pharmacology ; Endocrine System ; drug effects ; physiology ; Endothelins ; blood ; Fatigue ; blood ; physiopathology ; prevention & control ; Fatty Alcohols ; pharmacology ; Free Radicals ; blood ; metabolism ; Heart ; drug effects ; physiology ; Male ; Malondialdehyde ; blood ; Motor Activity ; drug effects ; Physical Conditioning, Animal ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood

OBJECTIVETo observe the protective effect of verapamil pretreatment against cerebral ischemia-reperfusion injury in gerbils.

METHODSThirty-three Mongolian gerbils were randomized into the control group (group A, n=6, with sham operation), ischemia group (group B), and 3 verapamil groups (groups C, D, and E, n=7) with intraperitpneal verapamil injection (2 mg/kg) 48, 24 and 12 h before ischemia, respectively. In group A, the bilateral common carotid arteries were only exposed without clamping, and in the other 4 groups, the arteries were clamped for 20 min followed by reperfusion for 50 min. The gerbils were then decapitated and the forebrain cerebral cortex was removed to determine superoxide dismutase (SOD) and glutathione (GSH) activities and measure the contents of malondial dehyde (MDA), endothelin (ET) and calcitonin gene-related peptide (CGRP). The left forebrain cerebral cortex was sampled in each group to observe the ultrastructural changes under electron microscope.

RESULTSIn groups C and D, SOD activities were significantly higher than those in group B (P<0.05), and in group E, the SOD activity elevation was not statistically significant (P>0.05). In groups C, D and E, GSH activity was significantly higher than that in group B (P<0.05). MDA content was significantly lower in groups C and D than in group B (P<0.05), but comparable between groups E and B (P>0.05). ET content was also significantly lower in the pretreatment groups (P<0.05), but CGRP content higher (not statistically so, however) than those in group B. The more serious ultrastructural damage of the cerebral tissue was observed in group B, but only mild damage was found in the verapamil groups.

CONCLUSIONSVerapamil given 12-48 h before cerebral ischemia may protect the gerbils from cerebral ischemia-reperfusion injury by enhancing SOD, GSH activities and decreasing ET content.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; metabolism ; pathology ; prevention & control ; Endothelins ; metabolism ; Gerbillinae ; Glutathione ; metabolism ; Malondialdehyde ; metabolism ; Receptors, Calcitonin Gene-Related Peptide ; metabolism ; Reperfusion Injury ; complications ; metabolism ; pathology ; prevention & control ; Superoxide Dismutase ; metabolism ; Verapamil ; pharmacology

OBJECTIVETo study anti-atherosclerotic mechanisms of divided functional recipes of Dahuang Zhechong pill (DHZCP) in rabbits.

METHODThe atherosclerotic rabbit model was established by high fat feeding combined with immune endothelial injury. Male New Zealand rabbits were divided into 9 groups: normal control group, model control group, Danshen positive control group, and 6 DHZCP-divided groups including divided functional recipes No. 1, 2, 3 with low and high doses for each divided recipe. After intragastric administration for 60 days, blood lipids and serum MDA and NO levels and SOD activity and plasma ET concentration, and contents of hydroxyproline and proteins in the vascular wall were determined.

RESULTCompared with the model group, the level of blood lipids did not significantly change, serum MDA and ET levels, and the contents of hydroxyproline and proteins in the vascular wall significantly decreased (P < 0.05), and SOD activity and NO level increased in the divided functional recipes (all P < 0.05).

CONCLUSIONThe divided functional recipes of DHZCP can inhibit development of atherosclerosis via a non-lowering lipid mechanisms, including anti-peroxidation of lipids, protection of endothelial function, and decrease of formation of extracellular matrix by reducing synthesis of collage and protein on the vascular wall. Among them, the divided functional recipe No. 1 exhibits the most obvious effect.

Animals ; Aorta ; metabolism ; Atherosclerosis ; blood ; pathology ; prevention & control ; Cockroaches ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelins ; blood ; Hydroxyproline ; metabolism ; Lipids ; blood ; Male ; Malondialdehyde ; blood ; Materia Medica ; isolation & purification ; pharmacology ; Nitric Oxide ; blood ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Rheum ; chemistry ; Superoxide Dismutase ; blood

OBJECTIVETo observe the effects of sapindoside on blood pressure, Ang II, Ald, ET in the blood plasma and NO in the serum in renovascular hypertension rat.

METHODThe 2K1C (2 kidney 1 clap) hypertensive model rats were used and drugs had been given by ig. for 5 weeks. The blood pressure was measured at the 1, 3, 7, 14, 21, 28, 35 day after drug. At the end of 5th weeks, the Ang II, Ald, ET in the blood plasma and NO in the serum were measured.

RESULTSapindoside (H, M and L) by ig. for 5 weeks could significantly lower the blood pressure, increase the levels of NO in the serum, reduce the concentration of Ang II, Ald, ET in the blood plasma.

CONCLUSIONSapindoside plays an important role in decreasing the blood pressure of renovascular hypertension rat.

Aldosterone ; blood ; Angiotensin II ; blood ; Animals ; Antihypertensive Agents ; isolation & purification ; pharmacology ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelins ; blood ; Female ; Hypertension, Renovascular ; blood ; physiopathology ; Male ; Nitric Oxide ; blood ; Oleanolic Acid ; analogs & derivatives ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Sapindus ; chemistry ; Saponins ; isolation & purification ; pharmacology

OBJECTIVETo investigate the effects of Corocalm (shuguan capsule) on acute myocardial ischemia in anesthetized dogs and its possible therapeutic mechanism.

METHODSThe acute ischemia model was established by ligating the left anterior descending (LAD) artery. Twenty-five dogs were randomly divided into 5 groups (5 dogs in each group): the control group (treated with normal saline 3 mL/kg), the refined Guanxin Capsule group (GXC 200 mg/kg), high and low dose Corocalm groups (48.5 mg/kg for low dose group and 194.0 mg/kg for high dose group) and the Diltiazem group (5 mg/kg). The animals were treated via a single duodenal administration after the model was established. The experiments used epicardial electrocardiogram (EECG) to measure the scope and degree of myocardial ischemia. Simultaneously, the coronary blood flow (CBF) and serum activity levels of creatine phosphokinase (CK) and lactate dehydrogenase (LDH) were measured by electromagnetic flow meter and automatic biochemical analyzer respectively. The plasma endothelin (ET) content was quantified by radioimmunoassay.

RESULTSCorocalm (48.5 mg/kg and 194.0 mg/kg) significantly decreased the degree and scope of myocardial ischemia, reduced the infarct area, markedly increased the CBF, and inhibited the increase of CK and LDH activities and ET levels induced by myocardial ischemia/infarction.

CONCLUSIONCorocalm could improve the state of acute myocardial ischemia and infarction in dogs. The mechanism of action might be correlated to increasing CBF, inhibiting CK and LDH activities and preventing ET release.

Anesthesia ; Animals ; Capsules ; Coronary Circulation ; drug effects ; Creatine Kinase ; blood ; Dogs ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelins ; blood ; Female ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardial Ischemia ; drug therapy ; pathology

AIMTo investigate the effects of pravastatin on endothelin(ET) expression induced by aldosterone in cultured neonatal rat cardiac fibroblasts.

METHODSET concentration in conditioned medium was measured by radioimmunoassay, intracellular ET-1 level was evaluated by flow cytometry, and the expression of preproendothelin-1 (ppET-1) was detected and quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) method.

RESULTSThe cardiac fibroblasts, treated with aldosterone at 107 mol/L, significantly up-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release. Pravastatin (10(-5), 10(-4), 10(-3) mol/L) dose-dependently blocked these effects. In contrast, pravastatin-induced inhibitory effects were reversed in the presence of mevalonate.

CONCLUSIONPravastatin down-regulated ppET-1 mRNA expression, as well as ET-1 synthesis and release induced by aldosterone in a process specifically related to mevalonate in cardiac fibroblasts.

Aldosterone ; metabolism ; Animals ; Cells, Cultured ; Endothelins ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Myoblasts, Cardiac ; drug effects ; metabolism ; Pravastatin ; pharmacology ; Rats ; Rats, Sprague-Dawley