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

BACKGROUND: To clarify the effect of hypoxia on vascular contractility, we tried to show whether hypoxia induced the release of endothelium-derived relaxing factor (EDRF) and the nature of the underlying mechanism for this release. MATERIAL AND METHOD: Isometric contractions were observed in rabbit aorta, and the released EDRF from the rabbit aorta was bioassayed by using rabbit denuded carotid artery. The intracellular Ca2+ concentration ([Ca2+]i) in the cultured rabbit aortic endothelial cells was recorded by a microfluorimeter with using Fura-2/AM. Hypoxia was evoked to the blood vessels or endothelial cells by eliminating the O2 in the aerating gases in the external solution. Chemical hypoxia was evoked by applying deoxyglucose or CN-. RESULT: Hypoxia relaxed the precontracted rabbit thoracic aorta that had its endothelium, and the magnitude of the relaxation was gradually increased by repetitive bouts of hypoxia. In contrast, hypoxia-induced relaxation was not evoked in the aorta that was denuded of endothelium. In a bioassay experiment, hypoxia released endothelium-derived relaxing factor (EDRF) and the release was inhibited by L-NAME or the K+ channel blocker tetraethylammonium (TEA). In the cultured endothelial cells, hypoxia augmented the ATP-induced increase of the intracellular Ca2+ concentration ([Ca2+]i) and this increase was inhibited by TEA. Furthermore, chemical hypoxia also increased the Ca2+ influx. CONCLUSION: From these results, it can be concluded that hypoxia might induce the release of NO from rabbit aortic endothelial cells by increasing [Ca2+]i.
Anoxia ; Aorta ; Aorta, Thoracic ; Biological Assay ; Blood Vessels ; Carotid Arteries ; Deoxyglucose ; Endothelial Cells ; Endothelium ; Endothelium-Dependent Relaxing Factors ; Gases ; Isometric Contraction ; NG-Nitroarginine Methyl Ester ; Nitrous Oxide ; Relaxation ; Tea ; Tetraethylammonium

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 explore the relationship of Chinese medicine (CM) syndrome with carotid intima-media thickness (CIMT) and endothelium-dependent vasodilatation function (EDVF) in patients with hypertensive disease (HD) for providing an objective basis of syndrome differentiation in HD patients.

METHODSColor Doppler's ultrasound was used to measure the endothelium-dependent flow-mediated dilation (FMD) of brachial artery and carotid intima-media thickness (CIMT) in 60 HD patients (the HD group) and 30 normal controls (the control group). And the relationship of the outcomes with Chinese medicine syndrome types in patients was analyzed statistically.

RESULTSFMD was lower and CIMT was higher in HD patients of all syndrome types than those in the control group respectively (P<0.01). Comparison between patients of different syndrome types showed that FMD was higher in patients of Gan-fire exuberance type and yin-deficiency and yang-hyperaction type than in those of both yin-yang deficiency type and phlegm-dampness stagnancy type (P<0.01, P<0.05), while CIMT in patients of Gan-fire exuberance type was the lowest in all types, and that in yin-deficiency and yang-hyperaction type was lower than in yin-yang deficiency type (P<0.01).

CONCLUSIONCIMT and FMD may be used as a reference index for CM syndrome differentiation in HD patients.

Adult ; Aged ; Carotid Intima-Media Thickness ; Case-Control Studies ; Endothelium-Dependent Relaxing Factors ; Female ; Humans ; Hypertension ; diagnosis ; diagnostic imaging ; physiopathology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Tunica Intima ; diagnostic imaging ; Tunica Media ; diagnostic imaging

AIMTo explore the resistant arterial effect of superoxide anion and its possible mechanisms.

METHODSThe third branch of the superior mesenteric artery in male Sprague-Dawley (200-300 g) rats was rapidly excised. Periadventitial fats and connective tissues were removed and the artery was dissected into about 2 mm rings. Each ring was dispensed between two stainless steel wires (diameter 0.0394 mm) in a 5 ml organ bath (DMT 610 M, Danish Myo Technology, Denmark). Isometric force recording studies in vitro of rat mesenteric arterial rings were recorded by Powerlab Syetem. Exposure of arteries to superoxide was accomplished through the auto-oxidation of pyrogallol added to the artery baths. Then endothelium-dependent or independent relaxation was investigated, respectively.

RESULTSExposure to pyrogallol (10, 100, 300, and 1 000 micromol/L) which could produce superoxide anion for 15 min resulted in a dose-dependent manner in a decrease of acetylcholine(ACh)-induced relaxation in rat mesenteric artery. Especially, the two predominant components of acetylcholine(ACh)-induced endothelium-dependent relaxation, EDHF component and NO component were both inhibited by superoxide anion from pyrogallol. However, exposure to superoxide anion from pyrogallol had no effect on the endothelium-independent relaxations to pinacidil or sodium nitroprusside (SNP) in rat mesenteric artery.

CONCLUSIONThese results indicate that superoxide anion can inhibit the endothelium-dependent relaxation in rat mesenteric artery, but has no effect on the endothelium-independent relaxation, in which the inhibited effect of EDHF and NO from endothelium is involved.

Acetylcholine ; pharmacology ; Animals ; Endothelium-Dependent Relaxing Factors ; physiology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; physiology ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley ; Superoxides ; pharmacology ; Vasodilation ; physiology

Since a cyclooxygenase 2 (COX-2) inhibitor can reduce infarct size and improve contractility in ischemic myocardium, the aim of the present study was to explore whether COX-2 inhibitor nimesulide could protect myocardial function against oxidative stress injury in rat hearts, and to investigate the underlying mechanisms. The isolated rat hearts perfused by Langendorff method were exposed to 140 mumol/L of H2O2, and the cardiac contractility was measured. Then, the responses of coronary arteries, precontracted with U-46619, to the endothelium-dependent vasodilator serotonin (5-HT) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were evaluated. The results were as follows: (1) In hearts exposed to H2O2 for 20 min, the left ventricular developed pressure [LVDP, (54.8 +/- 4.0)%] and maximal rate of rise/fall of ventricular pressure [+/-dp/dt(max), (50.8 +/- 3.1)% and (46.2 +/- 2.9) %] were reduced compared with that in the control group (100%). After pretreatment with nimesulide (5 mumol/L) for 10 min before H2O2 perfusion, LVDP and +/-dp/dt(max) were enhanced to (79.9 +/- 2.8)%, (80.3 +/- 2.6)% and (81.4 +/- 2.6)%, respectively (P<0.01), and this was partially abolished by the nitric oxide synthase (NOS) inhibitor L-NAME [(60.2 +/- 2.1)%, (63.9 +/- 2.4)% and (63.1 +/- 2.9)%, respectively, P<0.01]. (2) The vasodilatation induced by 5-HT and SNP in H2O2-treated group was significantly less than that in the control group. Pretreatment with nimesulide for 10 min antagonized the decrease of endothelium-dependent vasodilatation in H2O2-treated group [(-22.2 +/- 4.2) % vs (-6.0 +/- 2.5) %, P<0.01], but had no effect on the decline of endothelium-independent vasodilatation [(-2.0 +/- 1.8)% vs (-7.0 +/- 3.5) %, P>0.05]. (3) Pretreatment with nimesulide for 10 min increased the NO production in H2O2-treated hearts [(2.63 +/- 0.40) vs (1.36 +/- 0.23) nmol/g protein, P<0.05], and this was inhibited by L-NAME. (4) Pretreatment with the selective COX-1 inhibitor piroxicam had no effect on LVDP and +/-dp/dt(max) in isolated hearts exposed to H2O2, but the left ventricular end diastolic pressure (LVEDP) was much higher than that in the group treated with H2O2 alone. Piroxicam did not influence the coronary resistance in H2O2-treated rat hearts. These data suggest that the COX-2 inhibitor nimesulide improves myocardial function in rat hearts suffering from oxidative stress, and this may be through an improvement in endothelium-dependent arterial relaxation and an enhancement of NO production in rat heart.
Animals ; Coronary Vessels ; Cyclooxygenase 2 Inhibitors ; Endothelium, Vascular ; Endothelium-Dependent Relaxing Factors ; Heart ; drug effects ; Hydrogen Peroxide ; Myocardial Reperfusion Injury ; Myocardium ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Serotonin ; Sulfonamides ; pharmacology ; Vasodilation ; Vasodilator Agents

Diabetic erectile dysfunction (DED) is a multifactor syndrome, which involves vascular disease, neuropathy, metabolic control, nutrition, endocrine disorders, psychogenic factors, and anti-diabetes drugs. Among all these factors, vascular disease plays a very important role. In the development of diabetic vasculopathy, some vasomotion factors and growth factors undergo conspicuous changes, which may be significantly correlated with the development of diabetic erectile dysfunction.
Angiotensins ; metabolism ; Diabetes Complications ; complications ; Endothelins ; metabolism ; Endothelium-Dependent Relaxing Factors ; metabolism ; Epoprostenol ; metabolism ; Humans ; Impotence, Vasculogenic ; etiology ; metabolism ; Male ; Nitric Oxide ; metabolism ; Penis ; physiopathology ; Vasoactive Intestinal Peptide ; metabolism

Wenpi decoction ameliorates the harmful factors of chronic renal failure, such as mesangial matrix and its cytokines, nuclear factor, endothelium-dependent relaxing factor, oxidative free raidical, apoptosis, lipide, protein, and blood rheology. Wenpi decoction is an effective agent for delaying the progression of chronic renal failure.
Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Disease Progression ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelium-Dependent Relaxing Factors ; metabolism ; Kidney Failure, Chronic ; metabolism ; pathology ; Mesangial Cells ; cytology ; NF-kappa B ; metabolism ; Plants, Medicinal ; chemistry ; Superoxide Dismutase ; metabolism

BACKGROUND AND OBJECTIVES: Nitric Oxide (NO) is an endogenous mediator first characterized as an endothelium-derived relaxing factor. It is now recognized as a key mediator in many physiological process such as vasodilatation, neurotransmission, host defense, and iron metabolism. However, much remains to be determined about the pathophysiological role of NO in the airway. Peroxynitrite, which is synthesized by NO, is the diret cause of cellular toxicity in inflammatory reaction. In this study, we investigated the cellular toxcity of peroxynitrite by the expression of Heat-shock proteins 70 (HSP 70) in normal human nasal epithelium (NHNE) at the inflammatory conditions MATERIALS AND METHODS: 3-Morpholinosydronimone clorhydrate which is a peroxynitrite donor was mixed in the media of cultured NHNE cell. RESULTS: HSP 70 was expressed at the peroxynitrite environment of cultured NHNE cells and HSP 70 mRNA was detected with a time-dependent increasing pattern. CONCLUSION: Peroxynitrite may have a cytotoxic effect, and inhibition of peroxynitrite synthesis may have an important role for controlling the cytotoxic and inflammatory conditions of rhinitis and sinusitis.
Endothelium-Dependent Relaxing Factors ; Epithelial Cells* ; HSP70 Heat-Shock Proteins ; Humans* ; Iron ; Metabolism ; Nasal Mucosa ; Nitric Oxide ; Peroxynitrous Acid* ; Physiological Processes ; Rhinitis ; RNA, Messenger ; Sinusitis ; Synaptic Transmission ; Tissue Donors ; Vasodilation

Administration, Inhalation ; Endothelium-Dependent Relaxing Factors ; pharmacology ; Humans ; Hypertension, Pulmonary ; drug therapy ; Nitric Oxide Donors ; administration & dosage ; therapeutic use ; Nitroglycerin ; administration & dosage ; therapeutic use ; Nitroprusside ; administration & dosage ; therapeutic use ; Phosphodiesterase Inhibitors ; administration & dosage ; therapeutic use