OBJECTIVETo observe the protective effect of metformin on the endothelial function and the mechanisms in rats with low-density lipoprotein (LDL) injection.

METHODSA single dose (4 mg/kg) of natural LDL was injected through the sublingual vein of rats to induce vascular endothelial dysfunction. Blood samples were then collected from the rats to detect the concentrations of malondialdehyde (MDA) and nitric oxide (NO), activity of superoxide dismutase (SOD) and serum lipid levels. The thoracic aorta of rats was obtained to assay acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelium-independent relaxation. The effects of metformin pretreatment on the endothelial functions in the rats were investigated.

RESULTSA single-dose LDL significantly inhibited ACh-induced EDR without affecting SNP-induced endothelial-independent relaxation. The injection decreased serum NO and elevated serum MDA level, but had no effect on serum lipid level. Metformin markedly attenuated LDL-induced inhibition of EDR, serum MDA elevation, and serum NO reduction without affecting the serum lipid levels.

CONCLUSIONMetformin provides protection against vascular endothelial dysfunction induced by LDL in rats, the mechanism of which is probably associated with protection of endothelium-dependent relaxation factor and inhibition of the oxidative stress.

Animals ; Endothelium, Vascular ; drug effects ; physiopathology ; Endothelium-Dependent Relaxing Factors ; metabolism ; Lipoproteins, LDL ; administration & dosage ; Male ; Malondialdehyde ; blood ; Metformin ; pharmacology ; Nitric Oxide ; blood ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Vasodilation ; drug effects ; physiology

OBJECTIVETo study the effects of iptakalim (IPT) on pressure-overload induced cardiac remodeling in rats, and investigate correlation between this protection effects and plasma PGI2 content.

METHODThe pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively: (1) sham group, (2) control group, (3) IPT 3 mg/kg group (IPT 3), (4) indomethacin 2 mg/kg group (Indo 2), (5) indomethacin 2 mg/kg + IPT 3 mg/kg group (Indo 2 + IPT 3). RM6000 eight channel physiological recorder was used to record haemodynamics index, heart weight was weighed and the cardiac remodeling index was calculated, HE stain and Masson's stain were employed to perform histological analysis, colorimetric method was used to detect the hydroxyproline content in cardiac tissue, radioimmunological method was used to measure the plasma PGI2 content.

RESULTSAfter 42 days of aortic banding, the hyperdynamic circulation state, cardiac remodeling and decreased plasma PGI2 content were observed in the model group compared with those in the sham group, which were effectively reserved by treatment with IPT 3 mg/kg. Single-use indomethacin led to further deterioration of this pathophysiological changes, however, combination administration of IPT 3 mg/kg prevented these from worsening characteristic by ameliorating hyperdynamic circulation state and cardiac remodeling, augmnent plasma PGI2 content.

CONCLUSIONIPT can significantly reverse abdominal aorta binding/pressure-overload induced cardiac remodeling, its mechanism may contribute to binding K(ATP) channel in endothelial cells, ameliorating endothelium cells function, augmenting PGI2 synthesis and secretion.

Animals ; Aorta, Abdominal ; surgery ; Constriction ; Endothelium, Vascular ; metabolism ; physiology ; Epoprostenol ; blood ; Hypertension ; blood ; physiopathology ; KATP Channels ; drug effects ; Male ; Propylamines ; pharmacology ; Rats ; Ventricular Remodeling ; drug effects

OBJECTIVEThe main objective of this study is to assess the the effect of simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential mechanisms.

METHODSAdult male Wistar rats were randomized into sham group (n = 12), I/R (90 min ischemia via coronary ligation/120 min reperfusion, n = 18) and I/R plus sim group (20 mgxkg(-1)xd(-1) sim pretreated via gavage beginning 3 days before I/R, n = 18). After reperfusion, area at risk/area of left ventricular (RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at risk (NA/RA) and area of myocardial infarction/area at risk (MIA/RA) were measured. Myocardium homogenate was used to determine the activity of eNOS, iNOS and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was performed to determine the positive index of NF-kappaB p65 in cardiomyocytes and arteriole.

RESULTSThe NR and myocardial infarction areas in I/R plus sim group were significantly smaller than those in I/R group (34.10 +/- 7.05 vs. 52.09 +/- 6.89, 78.80 +/- 7.60 vs. 90.13 +/- 5.72, each P < 0.05) while the ischemia area was similar between the 2 groups (P > 0.05). The myocardial activities of iNOS and MPO, the contents of NO and MDA were significantly lower while eNOS activity was significantly higher in I/R plus sim group than those in I/R group (5.02 +/- 1.64 vs. 9.19 +/- 2.89, 586.21 +/- 126.97 vs. 744.49 +/- 137.53, 257.72 +/- 93.43 vs. 384.10 +/- 40.68, 72.10 +/- 18.56 vs. 111.84 +/- 38.58, 7.08 +/- 1.74 vs. 3.72 +/- 0.98, all P < 0.05). The positive index of NF-kappaB p65 in cardiocytes and arteriole at left ventricular wall near the area of myocardial infarction was significantly lower in I/R plus sim group than that in I/R group (21.59 +/- 10.5 vs. 34.32 +/- 9.55, 27.27 +/- 13.19 vs. 44.91 +/- 15.06, each P < 0.05).

CONCLUSIONSimvastatin could improve myocardial NR after ischemia-reperfusion by attenuating endothelial dysfunction and inhibiting inflammation and neutrophil activation.

Animals ; Disease Models, Animal ; Endothelium, Vascular ; drug effects ; Male ; Myocardial Infarction ; drug therapy ; physiopathology ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; drug therapy ; Myocardium ; metabolism ; Rats ; Rats, Wistar ; Simvastatin ; pharmacology

OBJECTIVETo observe the effect of chronic psychological stress on vascular endothelial dysfunction rats and to explore the intervention and mechanism of Tongxinluo (TXL) on it.

METHODSForty male Wistar rats were randomly divided into the normal control group (with no modeling), the endothelial dysfunction group (the HCY group), the psychological stress group (the model group), and TXL group, ten in each group. Rats in the latter three groups were fed with 3% high methionine diet to duplicate vascular endothelial dysfunction (VED) model. In addition, chronic psychological stress was applied in VED rats using repeated binding method. TXL at the dose of 1.2 g/kg body weight was given by gastrogavage. The plasma endothelin (ET) and angiotensin II (Ang II), serum cortisone (CORT) were detected by radioimmunoassay. The serum nitric oxide (NO) was detected by nitrate reductase. Ultrastructural changes of aortic endothelial cells were observed by transmission electron microscope. Serum levels of norepinephrine (NE) and epinephrine (E) were detected by enzyme linked immunosorbent assay (ELISA).

RESULTSCompared with the plasma ET level and the serum NO level in the HCY group (161.70 +/- 13.96 pg/mL and 26.82 +/- 13.03 micromol/L), the plasma ET level obviously increased (178.25 +/- 21.85 pg/mL) (P < 0.05) and the serum NO level decreased (24.91 +/- 9.95 micromol/L, P > 0.05), levels of CORT, NE, and E obviously increased in the model group (all P < 0.05). Ultrastructural changes of aortic endothelial cells were obviously injured. Compared with the model group, the plasma ET level (154.74 +/- 13.27 pg/mL), Ang II, CORT, NE, and E obviously decreased (P < 0.05, P < 0.01), the serum NO level obviously increased (34.44 +/- 18.35 micromol/L, P < 0.05). Ultrastructural changes of aortic endothelial cells were obviously improved.

CONCLUSIONSChronic psychological stress could obviously aggravate endothelial injury in VED rats. TXL showed protection on the vascular endothelial structure and function.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Endothelin-1 ; blood ; Endothelium, Vascular ; drug effects ; physiopathology ; Male ; Nitric Oxide ; blood ; Rats ; Rats, Wistar ; Stress, Psychological ; drug therapy

This study was intended to explore the effects of endothelium-independent, direct smooth muscle relaxants(papaverine, verapamil) and endothelium-dependent vasodilators(acetylcholine, bradykinin, adenosine) on the isolated cavernosal smooth muscle strips taken from diabetic men with impotence. When smooth muscle contraction was evoked with norepinephrine for the study of relaxation to these vasodilators, the tension induced was similar in diabetic and non-diabetic men with importance. Papaverine showed the strongest relaxation response followed by verapamil, acetylcholine, bradykinin and adenosine both in non-diabetic and in diabetic men. Relaxation of the cavernosal tissues to endothelium-independent vasodilators was similar in non-diabetic and diabetic men. However, the relaxation response of the tissues to endothelium-dependent vasodilators was significantly reduced in the diabetic group compared with that in the non-diabetic group (p<0.05). In conclusion, the impairment of endothelium-mediated relaxation of cavernosal smooth muscle seems to play a more important role in the pathogenesis of diabetogenic impotence rather than the problem of smooth muscle itself. This finding forms a rational basis for the use of intracavernosal injections of vasodilators to induce endothelium-independent relaxation of the cavernosal smooth muscle in the patients with diabetogenic impotence.
Adult ; Comparative Study ; Diabetes Mellitus/*physiopathology ; Endothelium, Vascular/*physiology ; Human ; Impotence/*physiopathology ; In Vitro ; Male ; Middle Age ; Muscle Relaxation/drug effects ; Muscle, Smooth/*drug effects/physiology ; Penis/*physiopathology ; Vasodilator Agents/*pharmacology

OBJECTIVEThe study investigate the antioxidant probucol on endothelial function in patients with acute coronary syndrome (ACS).

METHODSA total of 49 ACS patients randomly received standard therapy plus probucol (P, n = 24) or standard therapy (C, n = 25). Plasma oxidized low-density lipoprotein (ox-LDL), nitric oxide (NO) and circulating endothelial cells (CEC) were measured. The brachial arterial hyperemia-induced flow mediated dilation (FMD) and sublingual nitroglycerin (NTG) mediated vasodilatations were measured by high resolution ultrasound. These variables were analyzed before and after 3 months therapy.

RESULTSPlasma NO and FMD was significantly increased after 3 months therapy than before therapy [(80.46 +/- 10.24) micromol/Lvs (48.46 +/- 12.24) micromol/L, P < 0.01; (13.46 +/- 1.20)% vs (7.45 +/- 1.02)%, P < 0.05, respectively], while the number of CEC and ox-LDL were significantly decreased (P < 0.01) in P group. These values were similar before and after 3 months in C group. The linear correlation analysis showed that plasma ox-LDL negatively correlated with NO (r = -0.574, P < 0.01) and FMD (r = -0.517, P < 0.01) and positively correlated with CEC (r = 0.385, P < 0.01) in patients received 3 months probucol therapy.

CONCLUSIONSChronic antioxidant probucol therapy could improve endothelial function in patients with ACS.

Adult ; Aged ; Angina, Unstable ; blood ; drug therapy ; Anticholesteremic Agents ; therapeutic use ; Endothelial Cells ; drug effects ; physiology ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Humans ; Lipoproteins, LDL ; blood ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; physiopathology ; Nitric Oxide ; blood ; Probucol ; therapeutic use

OBJECTIVETo study the effect of Shengmai injection (, SMI) on vascular endothelial and heart functions in coronary heart disease patients complicated with diabetes mellitus (CHD-DM).

METHODSOne hundred and twenty patients with CHD-DM, their diagnosis confirmed by coronary arteriography, were equally randomized into a control group treated with conventional treatment and a treated group treated with conventional treatment plus SMI. The changes in blood levels of nitric oxide (NO), endothelin-1 (ET-1) and angiotensin II (Ang II), as well as endothelium-dependent vascular dilating function and heart function in the patients were observed before treatment and after the 3-week treatment.

RESULTSAfter being treated with SMI for 3 weeks, in the treated group, blood level of NO was raised significantly from 69.8 + or - 33.1 micro mol/L to 120.1 + or - 50.8 micro mol/L, and ET-1 was lowered from 70.1 + or - 32.1 ng/L to 46.2 + or - 21.3 ng/L, respectively (P<0.01); that of Ang II was lowered from 81.3 + or - 24.3 ng/L to 50.2 + or - 27.3 ng/L (P<0.01); brachial arterial post-congestion blood flow increasing rate was raised from 389.4 + or - 26.3% to 459.3 + or - 27.8% (P<0.01); and the improvement in heart function as seen through the ejection fraction (EF) was increased from 44 + or - 5% to 68 + or - 6% (P<0.01), all the changes being more significant than those in the control group (all P<0.01).

CONCLUSIONSMI can improve not only the endothelial function in CHD-DM patients, but also heart contraction significantly.

Coronary Disease ; drug therapy ; physiopathology ; Diabetes Complications ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelium, Vascular ; drug effects ; physiology ; Female ; Heart ; drug effects ; physiology ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the effect of Astragalus membranaceus (AM) on endothelial-dependent (EDV) and non- dependent (EIV) vascular relaxation in ex vivo thoracic aortic rings of obese rats.

METHODSFifteen SD rats were randomized into 3 equal groups, namely the control group fed with normal chow, obese group with high-fat chow, and AM intervention group fed with high-fat chow and daily AM gavage. The rats were sacrificed after 6 weeks of feeding, and the aortic rings were dissected and cut into 3-mm rings. The response to acethylcholine (Ach) and sodium nitroprusside (SNP) were examined in organ bath. In ex vivo study, the aortic rings obtained from the control group and obese group were incubated with AM or vehicle for 3 h in organ bath before testing the EDV and EIV. The body weight and weight of the visceral fat in each group were recorded.

RESULTSThe weight of visceral fat was greater in the obese group than in the control group, and a 6-week AM treatment significantly reduced the fat tissue due to high-fat diet. The maximum EDV value was (87.0 - or + 3.5)% in the control group, (54.8 - or + 7.8)% in the obese group, and (69.8 - or + 5.7)% in AM intervention group; the EIV values were comparable between the 3 groups. After incubation with AM, the maximum EDV values of aortic rings obtained from the obese group were significantly increased from (55.6 - or + 8.3)% to (85.1 - or + 4.5)%.

CONCLUSIONAM can improve endothelial dysfunction in obese rats, and the mechanism involves improved insulin resistance and increased endothelium-derived NO productor function.

Animals ; Aorta, Thoracic ; pathology ; Astragalus membranaceus ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Endothelium-Dependent Relaxing Factors ; therapeutic use ; In Vitro Techniques ; Insulin Resistance ; Male ; Obesity ; physiopathology ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Vasodilator Agents ; pharmacology

To observe the effect of Jiangzhikangyanghua Mixture on high-sensitivity CRP (hs-CRP) and vascular endothelial functions of essential hypertension (EH) patients. In this study, 72 cases of out-patients with EH were selected from department of cardiology of Wujin hospital of traditional Chinese Medicine, and randomly divided into the control group (n= 36, amlodipine 5 mg qd + valsartan 80 mg qd) and the test group (n =36 amlodipine 5 mg qd + valsartan 80 mg qd + Jiangzhikangyanghua mixture 20 mL tid). The contents of hs-CRP, ET-1 and NO were measured before and after treatment for two months. The result showed that the contents of hs-CRP, ET-1 in both groups reduced (P <0. 05) , while the test group show a more significant reduction than the control group (P <0. 05). After the treatment, the content of NO raised in both group, while the test group show a more significant increase than that of the control group (P <0. 05). This study indicated that Jiangzhi Kangyanghua mixture could reduce the contents of hs-CRP and ET-1 and raise NO of EH patients.
Aged ; Antihypertensive Agents ; administration & dosage ; Blood Pressure ; drug effects ; C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Endothelin-1 ; metabolism ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Humans ; Hypertension ; drug therapy ; metabolism ; physiopathology ; Male ; Middle Aged

AIMTo observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected.

METHODSHealthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected.

RESULTSCompared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P < 0.01), the format and percentage that capillary dilated declined significantly (P < 0.05), after treatment with Tongxinluo powder, the effect of Ach on isolated rat thoracic aorta in vitro was improved obviously (p < 0.01), and the format and percentage that capillary dilated were increased compared with model group; comparing with the control group, the level of Ang II and ET, TXA2 in plasm increased obviously (P < 0.05, P < 0.01), while the content of PGI2 depressed manifestly (P < 0.05), at the same time, both content of NO and activity of SOD, (GSH-PX declined obviously (P < 0.001, P < 0.05). After treatment with Tongxinluo powder, the level of ET, AngII and TXA2 reduced significantly in different degree (P < 0.01), while the content of PGI2 appeared stepping up notably (P < 0.01), and both activity of SOD and NO level increased obviously (P < 0.01, P < 0.05).

CONCLUSION(1) The high homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.

Animals ; Aorta ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Homocysteine ; antagonists & inhibitors ; pharmacology ; Male ; Protective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar