Animals ; Aorta, Thoracic ; physiology ; Dopamine ; pharmacology ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Rats ; Vasoconstriction ; drug effects

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

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 ; Aorta, Thoracic ; drug effects ; Atherosclerosis ; drug therapy ; Cholesterol ; blood ; Lipoproteins, LDL ; blood ; Opuntia ; chemistry ; Phytotherapy ; Rats ; Triglycerides ; blood

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

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

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

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 ; Animal ; Aorta, Thoracic/physiology ; Aorta, Thoracic/injuries ; Aorta, Thoracic/drug effects* ; Balloon Dilatation/adverse effects ; 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

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

OBJECTIVETo compare the difference of vasomotor functions in aortas segments from Wistar rats between 1-hour and 6-hours after exposure of water-soluble components of fine particulate matter (PM2.5).

METHODSAll 30 Wistar rats were assigned to five groups (n=6 for each group) at random: the blank control group, control group for 1-hour and 6-hours, exposure group for 1-hour and 6-hours. The rats were sacrificed 1-hour or 6-hours later and aorta ring segments were mounted on wire myographs.

RESULTS(1) There was no significant difference in vasomotor functions among three control groups (P>0.05). (2) 1-hour or 6-hours after exposure there was a decrease of contraction elicited by 60 mmol/L KCl in contrast to the control group (P<0.05), whereas no significant change between the exposure group for 1-hour and 6-hours (P>0.05). (3) On the level of 10(-5) or 10(-7) mol/L, 1-hour after exposure there was a decrease in endothelium-dependent acetylcholine (ACh) elicited relaxation precontracted by 10(-6) mol/L NE compared with the control group (P<0.01 or P<0.05), on the level from 10(-5) to 10(-7) mol/L there was a decrease compared with the exposure group for 6-hours (P<0.05), whereas no difference between the exposure group for 6-hours and the control group (P>0.05). On the level from 10(-5) to 10(-9) mol/L, 1-hour after exposure there was a decrease in endothelium-independent sodium nitroprusside (SNP) elicited relaxation precontracted by 10(-6) mol/L NE as compared with the control group (P<0.01 or P<0.05) and a decrease on the level of 10(-6) or 10(-9) mol/L compared with the exposure group for 6-hours (P<0.05), 6-hours after exposure a decrease was caused as compared with the control group on the level from 10(-5) to 10(-7) mol/L (P<0.01 or P<0.05).

CONCLUSIONSInhibition of contraction and impairment of relaxation in aortas should be caused 1-hour after exposure to water-soluble components of PM2.5 in the air, which is weaken 6-hours after exposure.

Acetylcholine ; blood ; Air Pollutants ; toxicity ; Animals ; Aorta, Thoracic ; Male ; Particulate Matter ; toxicity ; Rats ; Rats, Wistar ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects

OBJECTIVETo observe the effects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta rings of normoxic and chronic intermittent hypobaric hypoxic (CIHH) rats, and to investigate the underlying mechanisms.

METHODSYoung male Sprague-Dawley rats were randomly divided into normoxic group and CIHH group: the fonnrmer were not given any special treatment; the latter were exposed to hypoxia in a hypobaric chamber simulating 5000 m altitude (PB = 404 mmHg, PO2 = 84 mmHg, 11.1% O2), 6 hours daily for 28 days. The isolated thoracic aorta rings of rats were prepared and perfused in thermostat, and the effects of Coptis on vasoconstrictive activity of aorta rings were recorded, the mechanisms were investigated simultaneouly.

RESULTSCoptis Chinensis significantly decreased NE and KC-induced vasoconstriction of normoxic and CIHH rats' isolated aortic rings, but the inhibitive effects had no obvious discrepancy between the two groups. The contractive amplitude had no marked change after the removal of endothelium. When calculated by Logit Loglinear analysis, IC50 of NE and KCl-induced contractive amplitude in normoxic group were respectively 2.99 g/L and 6.14 g/L, while they were 3.45 g/L and 5.81 g/L in CIHH group. The inhibitive effect of Coptis on vasoconstrictive activity of both groups could be partly decreased by Glibenclamide and nitro-L-arginine methyl ester; Indomethacin suppressed the effect on normoxic group as well. Also Coptis significantly inhibited NE-induced both intracellular and extracellular calciumion-depended vasoconstriction.

CONCLUSIONCoptis Chinensis obviously relaxes isolated thoracic aorta rings of normoxic and CIHH rats, but the effects are endothelium-independent and have no marked discrepancy between the two groups. The mechanisms of the effects may be related to the opening of ATP-sensitive K+ channel, raise of nitric oxide concentration in both groups, and the increasing of PGI2 in normoxic group. Besides, Coptis may inhibit sarcoplasmic reticulum releasing Ca2+ and decrease the inflow of extracellular Ca2+ via cell membrane.

Animals ; Aorta, Thoracic ; physiopathology ; Calcium ; metabolism ; Coptis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Hypoxia ; physiopathology ; In Vitro Techniques ; KATP Channels ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects