Vasodilating properties of the stem bark extract of Mitragyna ciliata in rats and guinea pigs

Mitragyna ciliata is commonly used in traditional medicine for the treatment of inflammation, hypertension, headache, rheumatism, gonorrhoea and broncho-pulmonary diseases. In the present study, the vascular relaxant effect in the rat and guinea-pig was investigated. The extract induced aortic relaxation in a concentration-dependent manner, with an EC(50) of 1.3 and 7 microg/mL for the noradrenaline- and KCl-induced contractions, respectively. The relaxant effect of the extract on KCl-induced contractions was fi ve times greater than on noradrenaline-induced contractions. Moreover, the relaxant effect of the extract was higher in rat aortic rings with endothelium (104.67%) than without endothelium (49.44%). Chemical analysis of the extract showed the presence of alkaloids and flavonoids which may be responsible for the antihypertensive properties.     

葛根素的非内皮依赖性血管舒张作用机制

目的 :研究葛根素对血管的舒张作用并探讨其机制。方法 :记录离体大鼠胸主动脉环张力反应。结果 :葛根素能明显舒张由苯肾上腺素诱导收缩的大鼠主动脉环 ,其血管舒张作用为非血管内皮依赖性 ;KCl预收缩下 ,葛根素对主动脉环无舒张作用。对去内皮的血管环 ,在无Ca²⁺ 溶液中 ,葛根素不能够抑制咖啡因或苯肾上腺素诱导的短暂收缩。钾通道阻断剂 4 氨基吡啶和四乙胺孵育后能够明显抑制葛根素的舒张血管\作用 ,但格列苯脲不能抑制其舒张血管作用。结论 :葛根素的血管舒张作用是非内皮依赖性的 ,其机制可能是通过抑制α肾上腺素受体介导的血管平滑肌细胞外Ca²⁺ 内流而起作用的。同时 ,KV 通道和ATP敏感性K⁺ 通道参与了葛根素的舒血管作用。     

Vasorelaxant effect of stilbenes from rhizome extract of rhubarb (Rheum undulatum) on the contractility of rat aorta

The vascular relaxant effect of the rhizome extract of Rheum undulatum was evaluated with isolated rat thoracic aorta preparations. The methanol extract of the rhizome induced a concentration-dependent relaxation of aortic preparations precontracted with 0.3 microm phenylephrine (EC50 value: 5.8 microg/mL). The activity-guided fractionation of the extract led to the isolation of seven hydroxystilbene components as active principles, i.e. piceatannol, resveratrol, desoxyrhapontigenin, rhapontigenin, piceid, rhaponticin and epsilon-viniferin. Of these, piceatannol, a tetrahydroxystilbene, exhibited the most potent vascular relaxant effect in rat aortic preparations (EC50 value 2.4 microm). The vasorelaxant effect of piceatannol on endothelium-intact aorta rings was diminished completely by the removal of functional endothelium or by pretreatment of the aortic tissues with N(G)-nitro-l-arginine methyl ester. These results suggest that piceatannol may be the major mediator responsible for the vasorelaxing properties of the rhizome extract of Rheum undulatum and the vasorelaxant effects of the piceatannol may be mediated via endothelium-dependent nitric oxide signaling pathway.     

Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces

Previous studies have demonstrated the anti-hypertensive effects of Hibiscus sabdariffa L. (HS) in both humans and experimental animals. To explore the mechanisms of the anti-hypertensive effect of the HS, we examined the effects of a crude methanolic extract of the calyces of HS (HSE) on vascular reactivity in isolated aortas from spontaneously hypertensive rats. HSE relaxed, concentration-dependently, KCl (high K(+), 80 mM)- and phenylephrine (PE, 1 microM)-pre-contracted aortic rings, with a greater potency against the alpha(1)-adrenergic receptor agonist. The relaxant effect of HSE was partly dependent on the presence of a functional endothelium as the action was significantly reduced in endothelium-denuded aortic rings. Pretreatment with atropine (1 microM), L-NAME (10 microM) or methylene blue (10 microM), but not indomethacin (10 microM), significantly blocked the relaxant effects of HSE. Endothelium-dependent and -independent relaxations induced by acetylcholine and sodium nitroprusside, respectively, were significantly enhanced in aortic rings pretreated with HSE when compared to those observed in control aortic rings. The present results demonstrated that HSE has a vasodilator effect in the isolated aortic rings of hypertensive rats. These effects are probably mediated through the endothelium-derived nitric oxide-cGMP-relaxant pathway and inhibition of calcium (Ca(2+))-influx into vascular smooth muscle cells. The present data further supports previous in vivo findings and the traditional use of HS as an anti-hypertensive agent.     

原花青素舒张家兔主动脉和降低动脉血压的研究

目的：研究葡萄籽提取物原花青素(procyanidins，PC)舒张家兔离体主动脉和降低其动脉血压的作用及机制。方法：采用家兔离体胸主动脉环灌流模型，将标本分6组：去内皮、内皮完整、吲哚美辛(1×10^-1 mol·L^-1)、普萘洛尔(1×10^-5 mol·L^-1)、左旋硝基精氨酸N^ω-nitro-L-arginine(L-NNA 1×10^-4 mol·L^-1)或甲烯蓝(MB 1×10^-5 mol·L^-1)，分别累积加入1.25，2.5，5.0 mg·L^-1 PC观察血管张力变化；并观察40 mg·L^-1 PC对去甲肾上腺素（NA）(1×10^-8～1×10^-5 mol·L^-1)、KCl(6.3～100 mmol·L^-1)和CaCl₂ (1×10^-5～1×10^-2 mol·L^-1)诱导血管环收缩曲线的影响。另用家兔颈总动脉插管法，经静脉累积注射4.0，8.0，16，32，64，84 mg·kg^-1 PC后观察血压变化。结果：PC能舒张主动脉血管，并有量效依赖性(r=0.63，P<0.001)，去内皮、L-NNA或MB可减弱PC的舒张作用。PC能抑制NA，KCl和CaCl₂的量效收缩反应。PC能降低家兔正常动脉血压并有量效依赖性(r=0.92，P<0.001)。结论：PC舒张血管的作用是通过抑制细胞内Ca²⁺释放和电压依赖性Ca²⁺通道而减少Ca²⁺内流；也与内皮释放的NO有关；PC可降低家兔正常的动脉血压。     

The mechanism of vasorelaxation induced by ethanol extract of Sophora flavescens in rat aorta

Aim of the study

Sophora flavescens (SF) is a known medicinal herb for the treatment of cardiovascular symptoms associated with arrhythmia in China. However, the pharmacological action mechanisms involved have not been well studied. The aim of the present study was to define effects of roots of SF on the vascular tension and responsible mechanisms in rat thoracic aorta.

Materials and methods

Ethanol extract of the roots of SF (ESF) was examined for their vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aorta.

Results

ESF (0.1-100 μg/ml) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished the ESF-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with l-NAME, an inhibitor of nitric oxide synthase, and ODQ, an inhibitor of soluble guanylyl cyclase (sGC), inhibited ESF-induced vasorelaxation. ESF increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by l-NAME and ODQ. Inhibition of K⁺ channels with glibenclamide and tetraethylammonium, cyclooxygenase inhibition with indomethacin, and β-adrenergic and muscarinic receptors blockade had no effect on the ESF-induced vasorelaxation.

Conclusion

These findings suggest that ESF relaxes vascular smooth muscle via endothelium-dependent NO-sGC-cGMP signaling pathway.     

Water extract of Zanthoxylum piperitum induces vascular relaxation via endothelium-dependent NO-cGMP signaling

Aim of the study

The aim of the present study was to define the effects of extracts of leaves of Zanthoxylum piperitum (ZP) on the vascular tension and its mechanisms responsible in rat thoracic aortic rings.

Materials and methods

Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) were examined for their vascular relaxant effects in isolated phenylephrine-precontracted aortic rings.

Results

Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished the AZP-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with N^G-nitro-l-arginine methylester (L-NAME) and 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ) inhibited the AZP-induced vasorelaxation. Inhibition of Ca²⁺ entry via L-type Ca²⁺ channels failed to block the AZP-induced vasorelaxation. Extracellular Ca²⁺ depletion slightly but significantly attenuated the AZP-induced vasorelaxation. Thapsigargin significantly attenuated the AZP-induced vasorelaxation. Further, Gd³⁺ and 2-aminoethyl diphenylborinate (2-APB), inhibitors of store-operated Ca²⁺ entry (SOCE), markedly attenuated the AZP-induced vasorelaxation. Also, wortmannin, an inhibitor of Akt, an upstream signaling molecule of eNOS, attenuated the AZP-induced vasorelaxation. AZP increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by L-NAME, ODQ, thapsigargin, Gd³⁺, 2-APB, and wortmannin. K⁺ channel inhibition with glibenclamide and tetraethylammonium, cyclooxygenase inhibition with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the AZP-induced vasorelaxation.

Conclusion

Taken together, the present study suggests that AZP relaxes vascular smooth muscle via endothelium-dependent activation of NO-cGMP signaling through the Akt- and SOCE-eNOS pathways.     

Antiviral potency of mistletoe (Viscum album ssp. album) extracts against human parainfluenza virus type 2 in Vero cells

Various extracts from the leaves of mistletoe (Viscum album L. ssp. album) were investigated for their antiviral activity on human parainfluenza virus type 2 (HPIV-2) growth in Vero cells. Plant extracts were prepared using distilled water, 50% ethanol, petroleum ether, chloroform and acetone. The 50% effective dose (ED(50)) of aqueous extract for HPIV-2 replication was 0.53 +/- 0.12 micro g/mL, and the antiviral index (AI), which was based on the ratio of the 50% inhibitory concentration (CD(50)) for host cell viability to the ED(50) for parainfluenza virus replication, was 10.05. The aqueous extract was found to be the most selective inhibitor. Furthermore, the aqueous extract at a concentration of 1 micro g/mL was found to inhibit HPIV-2 replication and the virus production was suppressed to more than 99% without any toxic effect on host cells. The chloroform extract was also found to be moderately active. In an effort to further analyse the mechanism of antiviral activity, the effectiveness of the aqueous extract on different steps of virus replication was examined. The antiviral activity could neither be attributed to the direct inactivation of the HPIV-2 nor to the inhibition of adsorption to Vero cells. The active aqueous extract has shown a dose-dependent antiviral activity on virus replication.     

Vascular action of the crude hydroalcoholic extract from Hymenaea martiana on the isolated rat and rabbit aorta

The present study investigates the effect of the hydroalcoholic extract (HE) from Hymenaea martiana (Leguminosae) on endothelium-dependent and independent relaxation responses induced by acetylcholine (ACh), histamine (His), calcium ionophore (A23187) and sodium nitroprusside in precontracted aortic rings from rat and rabbit. In addition, we have also evaluated the action of the HE on noradrenaline- (NA), angiotensin I-(AI) and AII-induced contractions in the rabbit aorta. The HE (0.25–0.5 mg/mL) inhibited in a concentration-dependent manner the relaxant response induced by ACh in rings of rabbit aorta and by His in rat aorta. Relaxation in response to A23187 was inhibited in rat but not in rabbit aortic rings. In contrast, the HE was completely ineffective against endothelium-independent relaxations caused/by sodium nitroprusside in rabbit aorta rings. The HE (0.5–1.0 mg/mL) significantly enhanced the maximal contractile responses induced by NA in rabbit aorta set up with the endothelium, but caused no effect in endothelium rubbed preparations. In addition, the HE (0.5 mg/mL) markedly antagonized the contractile responses elicited by AI, but caused only a slight effect on AII-induced contractile responses in rabbit aorta. These findings indicate that the active principle(s) present in the HE from the bark of Hymenaea martiana selectively inhibit the endothelium-dependent vasorelaxant responses caused by several substances in aortic rings from rat and rabbit, presumably by a mechanism related with endothelium-derived relaxation factor synthesis and/or inactivation. The HE also antagonized AI but not AII-induced contractions in rabbit aorta, suggesting some interference with the angiotensin converting enzyme.     

大黄素对大鼠体外血管内皮一氧化氮cGMP信号途径的影响

目的探讨大黄素的舒血管效应与血管内皮一氧化氮cGMP信号途径的关系.方法采用MedLab生物信号采集系统记录灌流大鼠胸主动脉环张力变化;用硝酸还原酶法测定大黄素处理后离体大鼠主动脉血管的总一氧化氮合酶（tNOS）、结构型一氧化氮合酶（cNOS）、诱导型一氧化氮合酶（iNOS）活性的变化.结果大黄素对苯肾上腺素和氯化钾预收缩的内皮完整和去内皮血管环具有浓度依赖性的舒张作用.非特异性钾通道抑制剂氯化铯预处理能显著减弱大黄素对去内皮血管环的舒血管作用,但未能抑制大黄素对内皮完整血管环的舒血管作用.用一氧化氮合酶（NOS）抑制剂L-NAME和鸟苷酸环化酶抑制剂ODQ预处理后,40μmol/L大黄素引起的血管舒张作用被部分阻断,其血管舒张幅度分别为对照的（64.76±13.73）%和（6.28±4.79）%.40 μmol/L大黄素处理能够使血管iNOS的活性显著升高.结论大黄素的内皮依赖性舒血管作用可能通过激活血管内皮细胞中一氧化氮/cGMP信号途径而实现.     

五种中药提取物的血管活性作用实验研究

目的:观察川芎、大蓟、元参、红花和绞股蓝抽提物的血管活性作用。同时研究了绞股蓝的正丁醇、氯仿及水提取物对离体血管的影响。方法:实验是在有内皮和无内皮的离体大鼠主动脉上完成的。离体大鼠主动脉置于浴槽内,各种中药提取物所引起的血管张力改变被测定。结果:除红花外,其他4种中药引起剂量依赖性舒张作用,内皮存在时舒张反应更明显。绞股蓝的正丁醇提取物引起内皮依赖性扩张反应。而氯仿及水提取物无血管活性作用。结论:川芎、大蓟、元参、绞股蓝可引起内皮源舒张因子增加。红花无此作用。     

复方当归汤含药肠吸收液舒张血管平滑肌的研究

目的:研究复方当归汤含药肠吸收液舒张血管平滑肌的作用.方法:取大鼠小肠制成翻转囊,置于复方当归汤粗提液中温孵2h,取肠囊内K-R液即得复方当归汤含药肠吸收液.采用大鼠离体胸主动脉环灌流模型,观察累积浓度含药肠吸收液对基础状态、苯肾上腺素(PE)预收缩、氧化钾预收缩血管环的作用,并与硝苯地平比较.结果:复方当归汤含药肠吸收液对基础状态或氯化钾预收缩的血管环无明显影响;当含药肠吸收液中指标成分阿魏酸浓度累积达2.48 × 10-3,4.96×10-3,9.92×10-3g·L-1时,可剂量依赖性抑制PE预收缩的血管环收缩(P＜0.05).硝苯地平对基础状态预收缩的血管环无明显影响;当浓度累积达8.66×10-4,17.32 × 10-4,34.65 × 10 -4mmol·L-1时,可剂量依赖性抑制PE或氯化钾预收缩的血管(P＜0.05,或P＜0.01).结论:复方当归汤含药肠吸收液对完整内皮的PE预处理的血管有舒张作用,含药肠吸收液可用于中药复方离体药效学研究.     

Metabolites of the "smoke tree", Dalea spinosa, potentiate antibiotic activity against multidrug-resistant Staphylococcus aureus

Two new 2-arylbenzofuran aldehydes (1 and 2) and three known phenolic compounds (3-5) were isolated from organic extracts of Dalea spinosa. These compounds were evaluated for their intrinsic antimicrobial activity and their ability to perform as multidrug-resistance inhibitors by potentiating the activity of known antimicrobials against a variety of pathogenic microorganisms. Compound 1 and its acetate derivative 6 exhibited no direct antimicrobial activity but enhanced the effect of the weak plant antimicrobial berberine when tested against Staphylococcus aureus. Additional potentiation assays with S. aureus overexpression and knockout isogenic efflux mutants for the NorA pump were done in order to assess whether the potentiating effects were associated with inhibition of this known pump mechanism.     

Effects of the ethanolic extract of Spirulina maxima on endothelium dependent vasomotor responses of rat aortic rings

Dietary Spirulina decreases, endothelium-dependently, the responses to vasoconstrictor agonists and increases the endothelium-dependent, agonist-induced, vasodilator responses of rat aorta rings. The aim of this study was to analyze, in vitro, the effects of a raw ethanolic extract of Spirulina maxima on the vasomotor responses of rat aortic rings to phenylephrine and to carbachol. On rings with endothelium, the extract produced the following effects: (a) a concentration-dependent (60-1000 microg/ml) decrease of the contractile response to phenylephrine; (b) a rightward shift and a decrease in maximal developed tension, of the concentration--response curve to phenylephrine; (c) a concentration dependent relaxation of phenylephrine-precontracted rings. These effects were blocked by L-NAME, and not modified by indomethacin. The extract had no effect on the concentration-response curve to carbachol of rings with endothelium. On endothelium-denuded rings the extract caused a significant rightward shift of the concentration response curve to phenylephrine without any effect on maximal tension development. In the presence of the extract, indomethacin induced a marked decrease in the maximal phenylephrine-induced tension of endothelium-denuded rings. These results suggest that the extract increases the basal synthesis/release of NO by the endothelium and, also, the synthesis/release of a cyclooxygenase-dependent vasoconstricting prostanoid by vascular smooth muscle cells.     

Assessment of the antihypertensive and vasodilator effects of ethanolic extracts of some Colombian medicinal plants

The antihypertensive and vasodilator effects of ethanolic extracts prepared from Calea glomerata Klatt, Croton schiedeanus Schlecht, Curatella americana L., Lippia alba (Mill)n N.E.Br. and Lupinus amandus, which are medicinal plants used in Colombian folk medicine for the treatment of hypertension, were assayed both in SHR and Wistar rats and in rat isolated aortic rings. At a dose of 20 mg/kg, intravenous bolus administration of the ethanolic extracts, from C. schiedeanus, C. americana and L. amandus showed significant antihypertensive activity in SHR, C. schiedeanus being the most active. C. schiedeanus elicited dose-dependent decreases in mean arterial pressure and heart rate (5-100 mg/kg, i.v.) in SHR but 200 mg/kg administered orally did not show any significant effects, even after 3 h of observation. In intact rat aortic rings, ethanolic extracts from C. schiedeanus and Calea glomerata relaxed the contractions induced by KCl (80 mM) and phenylephrine (10(-6) M) in a concentration-dependent manner (10(-6)-3x10(-4) g/ml), with IC(50) of 6.5x10(-5) (7.3-5.8) g/ml and 7.1x10(-5) (7.9-6.4) g/ml, respectively. Bioguided phytochemical fractionation of the ethanolic extract from C. schiedeanus was started. More than one active principle seems to be present, flavonoids and terpenoids compounds were detected.     

Direct relaxant effects of garlic juice on smooth and cardiac muscles

The effects of garlic juice on smooth and cardiac muscles of rabbit and guinea pig were tested in vitro using isolated segments of aorta, trachea and intestines and isolated rabbit hearts. Garlic juice inhibited the contractions of rabbit and guinea pig aortic rings induced by norepinephrine in Ca(2+)-free and Ca(2+)-containing Krebs-Henseleit solutions. Also, garlic juice inhibited the contractions of rabbit and guinea pig tracheal smooth muscles induced by acetylcholine and histamine, respectively, in both Ca(2+)-free and Ca(2+)-containing Krebs-Henseleit solutions. Furthermore, garlic juice inhibited the spontaneous movements of rabbit jejunum and guinea pig ileum and inhibited the force of contraction of isolated rabbit hearts in a concentration-dependent manner. All inhibitions were reversible. These data suggest that the hypotensive action of garlic juice may be due, at least in part, to a direct relaxant effect on smooth muscles.     

Ellagic Acid‐Induced Endothelium‐Dependent and Endothelium‐Independent Vasorelaxation in Rat Thoracic Aortic Rings and the Underlying Mechanism

The present study first investigated the mechanisms of vasorelaxation induced by ellagic acid (EA), which is one of the major compounds extracted from the pomegranate in the rat thoracic aorta. Male Wistar rats aged 10 to12 weeks weighing 250–350 g were used for the present study. The animals were killed by decapitation, and thoracic aortas were immediately excised and placed in Krebs solutions, cleaned, and freed from surrounding connective tissue. The isolated arteries were cut into rings (4‐ to 5‐mm long) and placed in 20‐mL tissue chambers filled with Krebs solution. Initially, the aortic rings were equilibrated for 60 min until a resting tension of 1.0 gr. After the equilibration period, aortic rings were firstly contracted with phenylephrine to increase tone. Once a stable contraction was achieved, EA (10^?8 to 10^?4 M) was added cumulatively on aortic rings with or without endothelium into organ bath. To characterize the mechanisms involved in EA‐induced vasorelaxant effect, the aortic rings were incubated with each inhibitor added to the bath for 30 min before phenylephrine was added to increase tone. The results of the present study have demonstrated in the rat thoracic aorta that EA causes vasorelaxations, which are partly modulated via endothelium‐dependent mechanisms and through inhibition of calcium influx. Copyright © 2012 John Wiley & Sons, Ltd.     

Possible mechanisms of vasorelaxation for 5,7-dimethoxyflavone from Kaempferia parviflora in the rat aorta

The present study investigated the vascular effects of 5,7-dimethoxyflavone (DMF), isolated from the rhizomes of Kaempferia parviflora (KP), on rat isolated aortic rings and its possible mechanisms. DMF (1-100 μM) caused concentration-dependent relaxations in aortic rings precontracted with methoxamine. This effect was significantly reduced by removal of the endothelium, and after pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 300 μM), indomethacin (10 μM) and 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 μM), but not 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536, 100 μM). Relaxant responses to DMF were significantly inhibited by high KCl (60 mM) in both endothelium-intact and -denuded rings. In addition, the relaxations to DMF were significantly reduced by pretreatment with tetraethylammonium (TEA, 5 mM), glibenclamide (10 μM), 4-aminopyridine (1 mM) or barium chloride (10 μM). Preincubation with DMF (10 and 100 μM) for 30 min significantly inhibited the contractile responses to CaCl(2) in a Ca(2+)-free, high K(+) buffer. The present study demonstrated that DMF causes endothelium-dependent relaxation that is partly mediated by NO-cGMP and cyclooxygenase pathways. Interestingly, DMF-induced responses are mainly due to increasing K(+) efflux, and inhibition of Ca(2+) influx from the extracellular space. The vasodilator effects of DMF provide experimental support for the potential use of KP as a medical plant in the treatment of cardiovascular diseases.     

Vascular relaxation by ethanol extract of Xanthoceras sorbifolia via Akt- and SOCE-eNOS-cGMP pathways

Aim of the study

The aim of the present study was to define the effect of Xanthoceras sorbifolia extracts (XS) on vascular tension and responsible mechanisms in rat thoracic aortic rings.

Materials and methods

Ethanol extract of the leaves of XS (EXS) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta.

Results

EXS (0.1-100 μg/ml) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished EXS-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with N^G-nitro-l-arginine methylester (l-NAME) and 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ) inhibited EXS-induced vasorelaxation. Inhibition of Ca²⁺ entry via l-type Ca²⁺ channels failed to block the EXS-induced vasorelaxation. Extracellular Ca²⁺ depletion significantly attenuated EXS-induced vasorelaxation. Modulators of the store-operated Ca²⁺ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate (2-APB) and Gd³⁺, and an inhibitor of Akt, wortmannin, markedly attenuated the EXS-induced vasorelaxation. EXS increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by l-NAME, ODQ, thapsigargin, Gd³⁺, 2-APB, and wortmannin. Further, EXS-induced vasorelaxation was significantly attenuated by tetraethylammonium, a non-selective K_ca channels blocker, but not by glibenclamide, an ATP-sensitive K⁺ channels inhibitor. Inhibition of cyclooxygenase with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on EXS-induced vasorelaxation.

Conclusions

The present study suggests that EXS relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt- and SOCE-eNOS-sGC pathways, which may, at least in part, be related to the function of K⁺ channels.     

白藜芦醇对大鼠离体胸主动脉环的舒张作用

目的:观察白藜芦醇(resveratrol,RVL)对大鼠离体胸主动脉血管的舒张作用并探讨其机制。方法:采用离体血管环灌流方法,观察RVL在含Ca²⁺或无Ca²⁺ Krebs液孵育条件下对去甲肾上腺素(NA)引起的血管平滑肌收缩的影响;同法观察RVL对30,80mmol·L^-1的KCl引起的血管平滑肌收缩的影响;RVL对NA引起的依赖于细胞内钙和细胞外钙收缩反应的影响,以及加入N-G-硝基-L-精氨酸(L-NNA)和优降糖后RVL舒张大鼠离体主动脉环效应的变化。结果:RVL呈浓度依赖性舒张NA引起的血管收缩;无Ca²⁺ 组RVL抑制NA所致血管平滑肌收缩效应大于含Ca²⁺ 组;RVL能够拮抗NA诱发的依内钙的收缩反应,而对外钙收缩无抑制。RVL对80,30mmol·L^-1 的KCl引起的血管平滑肌收缩均有抑制作用,且前者量效曲线明显上移。L-NNA使RVL舒血管效应降低(26.0±4.6)%;优降糖组的血管舒张受抑程度与对照组无显著差别(P>0.05)。结论:RVL可呈内皮依赖性舒张血管平滑肌,其作用机制可能与该药促进NO合成释放,开放钙激活的钾通道以及抑制血管平滑肌细胞外钙内流和内钙释放有关。