2.Effect of heme oxygenase-1 on hydrogen peroxide induced hypo-responses in vascular contraction.
Li ZHU ; Ying-Ying CHEN ; Wei GUO ; Yang WANG ; He-Jing XU ; Yue-Liang SHEN ; Qiang XIA
Chinese Journal of Applied Physiology 2006;22(4):464-468
AIMTo examine the effect of HO-1 inducer hemin on hydrogen peroxide (H2O2) caused decrease in contraction of isolated rat aortic rings, and to elucidate the underlying mechanism.
METHODSThe thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured.
RESULTS(1) After intraperitoneal injection of HO-1 inducer hemin, HO-1 activity of thoracic aorta and COHb concentration in rat blood enhanced. And it also prevented the decrease in contraction responses to PE which pretreatment of arteries with 300 micromol/L H2O2. (2) Pretreatment of ATP-sensitive potassium channel inhibitor glibenclamide, but not GC inhibitor methylene blue, could partly abolish the protection of hemin in arteries with H2O2 exposure. (3) Hemin could not influence the shift of concentration-response curve to [Ca2+]o in arteries with H2O2 exposure. (4) In Ca(2+) -free K-H solution, exposure of H2O2 reduced caffeine and PE-induced constriction in the rat aortic rings. After pretreatment of hemin, could prevent the decrease in contraction responses to caffeine and PE.
CONCLUSIONIncrease in HO-1 activity could prevent the H2O2 induced decrease in contraction responses to PE in intact aortic rings. The mechanism might be involved in activation of ATP-sensitive potassium channel and mobilization of intracellular calcium stores, but had no relationship with the GC pathway.
Animals ; Aorta, Thoracic ; drug effects ; physiology ; Endothelium, Vascular ; Heme Oxygenase-1 ; pharmacology ; Hydrogen Peroxide ; adverse effects ; KATP Channels ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects
3.Therapeutic effects and mechanisms of Opuntia dillenii Haw on atherosclerosis of rats.
Yu-chun WANG ; Zhan-peng QI ; Zhen-zhong LIU ; Tao LI ; Hong-xia CUI ; Bao-qing WANG ; Na CHI
Acta Pharmaceutica Sinica 2015;50(4):453-458
The research aimed to investigate the therapeutic effects and mechanisms of Opuntia dillenii Haw polysaccharide (OPS) on atherosclerosis of rats. First atherosclerotic rat models were established by high-fat and high-calcium diet. Thirty days later, the rats were treated with low dosage of OPS (0.2 g x kg(-1) x d(-1)) or high dosage of OPS (0.4 g x kg(-1) x d(-1)) by intraperitoneal injection for 60 days continuously. At the end of treatment, thoracic aorta rings were prepared and vasorelaxation of rat thoracic aorta in different experiment groups were determined by using 620M multi wire myograph system in vitro. Blood and livers of rats were collected. Then plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) of rats were separately determined using whole automatic biochemical analyzer; protein level of hepatic apolipoprotein B (ApoB) and that of hepatic diglyceride acyltransferase (Dgat1) were measured by Western Blot technique. Results showed that the ability of rat thoracic aorta to relax decreased markedly in the model group compared with that in the normal group, and significant differences existed in vasorelaxation ratios induced by different concentrations of carbamylcholine chloride (Carb) between these two groups (P < 0.01). After OPS treatment, the ability of rat thoracic aorta to relax improved markedly, the vasorelaxation ratios induced by Carb at 5 and 10 μmol x L(-1) were respectively 0.34 ± 0.08 and 0.62 ± 0.15 in the group treated with low dosage of OPS, while the ratios induced by Carb at 1 and 5 μmol x L(-1) were respectively 0.54 ± 0.08 and 0.98 ± 0.02 in the group treated with high dosage of OPS, which were all significantly different with those in the model group (P < 0.01). Plasma contents of TC, TG and LDL reduced significantly by the treatments both with low and high dosages of OPS compared with those in the model group (P < 0.01). Protein level of hepatic ApoB and that of hepatic Dgat1 decreased significantly after the treatment with high dosage of OPS compared with those in the model group (P < 0.01). These results indicate that OPS can markedly improve the vasorelaxation of thoracic aorta of atherosclerotic rats and has significant anti-atherosclerotic effect; inhibiting the expression of ApoB and Dgat1 and thus decreasing the amounts of TC, LDL and TG serving as one of the molecular mechanisms of its antiatherosclerosis effect.
Animals
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Aorta, Thoracic
;
drug effects
;
Atherosclerosis
;
drug therapy
;
Cholesterol
;
blood
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Lipoproteins, LDL
;
blood
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Opuntia
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chemistry
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Phytotherapy
;
Rats
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Triglycerides
;
blood
4.Endothelium-independent vasorelaxation of plant-derived estrogen biochanin A and its mechanism in rat aortic rings.
Hui-ping WANG ; Fu-yu QIU ; Cheng CHEN ; Meng-hui ZHAO ; Yuan LU ; Qiang XIA
Chinese Journal of Applied Physiology 2006;22(3):274-277
AIMTo investigate the mechanisms of vasodilatation of plant-derived estrogen biochanin A.
METHODSIsolated aortic ring preparations from Sprague-Dawley rats were suspended in individual organ baths. The tension was measured isometrically.
RESULTSBiochanin A at the range of 10(-9)-10(-4) mol/L provoked concentration-dependent and endothelium-independent relaxation of the rings constricted by phenylephrine (10(-5) mol/L). Biochanin A caused concentration-dependent relaxation of denuded rings precontracted with KCl (6 x 10(-2) mol/L). Glibenclamide (3 x 10(-6) mol/L), a selective inhibitor of ATP-sensitive potassium channels, and tetraethylammonium (5 x 10(-3) mol/L), a Ca2+ -activated K+ channel inhibitor, significantly attenuated the relaxation induced by biochanin A. The vasoconstriction induced by phenylephrine was decreased by biochanin A in Ca2+ -free medium.
CONCLUSIONThe endothelium-independent relaxation of thoracic aorta induced by biochanin A might be mediated by ATP-sensitive K+ channels, Ca2+ -activated K+ channels and intracellular Ca2+ release from sarcoplasmic reticulum.
Animals ; Aorta, Thoracic ; drug effects ; physiology ; Genistein ; pharmacology ; In Vitro Techniques ; KATP Channels ; metabolism ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects
5.Effect of cinobufacini on vascular contractile of rat thoracic aorta.
Xu-yun LI ; Yuan LU ; Qi-xian SHAN ; Qiang XIA
Journal of Zhejiang University. Medical sciences 2006;35(2):178-181
OBJECTIVETo examine the effect of cinobufacini on rat thoracic aorta and its mechanism.
METHODSIsolated rat thoracic aorta was perfused and isometric tension was recorded by organ bath technique before and after cinobufacini treatment.
RESULTCinobufacini induced contraction of isolated thoracic aorta with or without endothelium in a concentration-dependent manner (at concentration of 2.5,5.0,7.5,10.0 g/L). The vasoconstriction effect of cinobufacini was more potent in endothelium-denuded aorta ring [(16.3+/-3.39)%, (52.5+/-7.70)%, (60.9+/-8.84)%, (69.2+/-11.34)%] than in endothelium-intact aorta ring [(6.2+/-2.07)%, (14.7+/-4.91), (17.6+/-5.86)%, (20.3+/-6.78)% (P<0.01)]. Its contractile effect was attenuated in Ca(2+)-free solution (about 1/10 of that in buffer with 1.25 mmol/L CaCl(2)) or by the treatment with verapamil (10(-7)mol/L), an L-type calcium channel antagonist. Cinobufacini induced contraction on the endothelium-intact rat aorta was augmented by pretreatment with L-NAME (10(-4)mol/L), a nitric oxide synthase inhibitor.
CONCLUSIONCinobufacini contracts rat thoracic aorta by opening the voltage-dependent Ca(2+) channel and increasing Ca(2+) influx into vascular smooth muscle. Cinobufacini can also stimulate the release of vascular relaxant factor, nitric oxide, from the endothelium and thus antagonize cinobufacini-induced contraction.
Animals ; Aorta, Thoracic ; drug effects ; Bufanolides ; pharmacology ; Endothelium, Vascular ; drug effects ; metabolism ; In Vitro Techniques ; Male ; Nitric Oxide ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects ; Vasoconstrictor Agents ; pharmacology
6.Lipid peroxidation and biomechanical properties of artery in hyperlipemia rats after treating with tetrahydrobiopterin.
Bao-Liang ZHU ; Rui-Zhen YAN ; Jiang YU ; Yan-Jun DONG
Chinese Journal of Applied Physiology 2011;27(4):461-464
OBJECTIVETo explore the effect of the level of lipid peroxidation and biomechanical properties after chronic treating with tetrahydrobiopterin (BH4) in thoracic aorta of hyperlipemia (HL) rats.
METHODSHL rats were given BH4 chronically. The opening angle in the zero-stress state and the relationship between pressure and diameter (P-D) of mesenteric artery were measured by computer image 8, 16, and 24 week-old respectively.
RESULTSTreating with BH4 chronically from 8 week-old in HL rats, there was a significant increase in the zero-stress state of opening angle of thoracic aorta. The P-D curve of mesenteric artery moved upward.
CONCLUSIONTreating with BH4 prevented the structure and function of artery from abnormal changing, and attenuated lipid peroxidation in HL rats.
Animals ; Aorta, Thoracic ; metabolism ; physiopathology ; Biomechanical Phenomena ; drug effects ; Biopterin ; analogs & derivatives ; therapeutic use ; Hyperlipidemias ; drug therapy ; Lipid Peroxidation ; drug effects ; Male ; Rats ; Rats, Wistar
7.All-trans-retinoic acid attenuates neointima formation with acceleration of reendothelialization in balloon-injured rat aorta.
Cheol Whan LEE ; Seung Jung PARK ; Seong Wook PARK ; Jae Joong KIM ; Myeong Ki HONG ; Jae Kwan SONG
Journal of Korean Medical Science 2000;15(1):31-36
Retinoic acids may inhibit vascular smooth muscle cell proliferation, but may promote endothelial cell proliferation in cell culture. However, little data are available about the effects of all-trans-retinoic acid (ATRA) on endothelial regeneration and functional recovery in an experimental model of vascular injury. Accordingly, we investigated whether ATRA may attenuate neointima formation and accelerate endothelial regeneration with functional recovery in balloon-injured rat aorta. Twelve-week-old male Sprague-Dawley rats underwent endothelial denudation of the thoracic aorta by balloon injury. Fourteen rats were fed a standard rat pellet diet. Another 14 rats were fed ATRA (1.5 mg/day) for 2 weeks. The animals were killed on day 14 for organ chamber study and morphometric analysis. Rats in the ATRA group had a significantly improved acetylcholine-induced relaxation response than those in control group. However, endothelial independent response was not significantly different between the two groups. The extent of reendothelialization was markedly superior in the ATRA group compared with control group (p>0.05). Furthermore, neointima area and the ratio of neointima to medial area were significantly less in ATRA group than in control group (p>0.05). In conclusion, ATRA may accelerate endothelial regeneration with functional recovery, and attenuate neointima formation in balloon-injured rat aorta.
Acetylcholine/pharmacology
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Animal
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Aorta, Thoracic/physiology
;
Aorta, Thoracic/injuries
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Aorta, Thoracic/drug effects*
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Balloon Dilatation/adverse effects
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Endothelium, Vascular/physiology
;
Endothelium, Vascular/drug effects
;
Male
;
Muscle Relaxation/physiology
;
Muscle Relaxation/drug effects
;
Muscle, Smooth, Vascular/physiology
;
Muscle, Smooth, Vascular/drug effects
;
Rats
;
Rats, Sprague-Dawley
;
Regeneration/physiology
;
Regeneration/drug effects
;
Tretinoin/pharmacology*
;
Tunica Intima/physiology
;
Tunica Intima/pathology*
;
Tunica Intima/drug effects*
;
Vasodilator Agents/pharmacology
8.Synthesis and vascular relaxing activity of arecoline derivatives coupled with nitric oxide donors.
Sheng-Tang HUANG ; Wen-Long HUANG ; Hui-Bin ZHANG
Acta Pharmaceutica Sinica 2006;41(1):71-75
AIMTo search for potential anti-atherosclerosis drugs with vascular relaxation activity, a series of agonists of endothelial targets were designed and synthesized.
METHODSCoupling N-methyl-1,2, 3,6-tetrahydrapyridine ring system with 3,4-dibenzenesulfonyl-1,2,5-oxadiazole-2-oxide through esterification or amidation, a series of arecoline derivatives containing NO donors were designed and synthesised.
RESULTSA novel series of compounds structurally related to arecoline have been prepared, the proposed structures of eighteen new compounds were established by IR, 1H NMR, MS spectroscopy and elemental analysis. The effects of the target compounds on the vasodilation activity were tested in the isolated preparation of mice thoratic aorta.
CONCLUSIONThis preliminary pharmacological tests showed that the candidates have good vasodilation activities and were worthy to be intensively studied.
Animals ; Aorta, Thoracic ; drug effects ; Arecoline ; analogs & derivatives ; chemical synthesis ; pharmacology ; In Vitro Techniques ; Nitric Oxide Donors ; chemistry ; pharmacology ; Rats ; Vasodilation ; drug effects ; Vasodilator Agents ; chemical synthesis ; pharmacology
9.Vasorelaxation effect of gastrodin on isolated thoracic aorta rings of rats.
Yuan-long XIE ; Min ZHOU ; Hui-hao MA ; Xiang WANG ; Ju-ju LIU
Chinese journal of integrative medicine 2015;21(12):944-948
OBJECTIVETo study the effect of gastrodin on isolated thoracic aorta rings of rats and to investigate the potential mechanism.
METHODSA perfusion model of isolated thoracic aorta rings of rats was applied. The effect of cumulative gastrodin (5, 50, 100,150, 200, and 250 μmol/L) on endothelium-intact aorta rings was investigated. The same procedure was applied to observe the effect of gastrodin on endothelium-intact/denuded aorta rings pre-contracted with 10(-6) mol/L phenylephrine hydrochloride (PE). The aorta rings incubated by 200 mmol/L gastrodin in the Ca(2+)-free (K-H) solution was contracted by using PE. The effect of 200 mmol/L gastrodin on endothelium-denuded aorta rings pre-contracted with 60 mmol/L KCl was also observed.
RESULTSCompared with the denuded gastrodin group, the intact gastrodin group could significantly relax the PE-contracted aorta rings (P<0.01). In Ca(2+)-free (K-H) solution KHS, the PE-induced contraction rate of aorta rings pre-incubated by gastrodin was 6.5%±0.7%, which was significantly less than the control group (11.8%±0.9%,P<0.01). However, after 3 mmol/L CaCl2 was added, the Ca(2+)-induced contraction in the gastrodin group (51.7%±2.4%) was similar to that in the control group (49.8%±2.8%). The contractile rate of rings in the KCl-contracted gastrodin group (96.3%±0.6%) was not significantly different from that in the control group (96.8%±1.2%).
CONCLUSIONSGastrodin has the effect of vasorelaxation on isolated thoracic aorta rings of rats. The mechanism of the vasorelaxation of gastrodin may mainly work through the inhibition of inositol 1, 4, 5-trisphosphosphate receptor on the sarcoplasmic reticulum of the arterial smooth muscle, which leads to the reduction of the Ca(2+) released from the sarcoplasmic reticulum.
Animals ; Aorta, Thoracic ; drug effects ; physiology ; Benzyl Alcohols ; pharmacology ; Calcium ; metabolism ; Endothelium, Vascular ; physiology ; Female ; Glucosides ; pharmacology ; In Vitro Techniques ; Male ; Phenylephrine ; pharmacology ; Rats ; Rats, Wistar ; Vasodilation ; drug effects
10.Effect and mechanism of puerarin on high glucose-induced hypo-responses in vascular contraction.
Yi-Miao ZHU ; Chao NI ; Li ZHU ; Yue-Liang SHEN ; Ying-Ying CHEN
Chinese Journal of Applied Physiology 2011;27(1):62-65
OBJECTIVETo examine the effect of puerarin on high glucose-induced decrease in contraction of isolated rat aortic rings, and to elucidate its underlying mechanism.
METHODSThe thoracic aortic rings with or without endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured. The activity of heme oxygenase-1 (HO-1) was also measured.
RESULTS(1) After incubation with 44 mmol/L of glucose (high glucose) for 4 h, the vascular contraction responses to phenylephrine (PE) decreased in an endothelium-dependent manner, when compared with the control group (containing 11 mmol/L of glucose). (2) After coincubation with puerarin ( 10(-10) - 10(-8) mol/L) and high glucose, the decrease in contraction responses to PE of arteries was partly inhibited in a dose-dependent manner. (3) After incubation with puerarin for 4 h, the HO-1 activity of thoracic aorta increased; ZnPP, an inhibitor of HO-1, abrogated the protection effect of puerarin.
CONCLUSIONPuerarin could prevent the high glucose-induced decrease in contraction responses to PE in intact aortic rings. The mechanism might be involved in the activation of HO-1.
Animals ; Aorta, Thoracic ; drug effects ; physiology ; Glucose ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; In Vitro Techniques ; Isoflavones ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects ; Vasodilator Agents ; pharmacology