Differential antagonistic effect of hydroalcoholic extract from Hymenaea martiana hayne arzeik on kinin and other agonist-induced contractions of the isolated rat uterus and Guinea-pig ileum

This study was undertaken to evaluate the action of the hydroalcoholic extract (HE) from the bark of Hymenaea martiana on bradykinin (BK), lysyl-bradykinin (L-BK), acetylcholine (ACh), angiotensin II (AII), prostaglandin F_2a (PGF_2a), serotonin (5-HT), oxytocin (Ot) and histamine (His)-induced contractions of the isolated rat uterine muscle and guinea-pig ileum. The HE (50–200 μg/mL) added to the bath for 20 min caused a concentration-dependent rightward displacement of BK, L-BK and ACh-induced contractions in the rat uterus, allied to a discrete but significant reduction of maximal responses to the latter two agonists. By contrast, at the same range of concentrations the HE antagonized in a concentration-dependent but noncompetitive manner the contractions induced by AII, but only at high concentrations (200 μg/mL) it significantly inhibited contractions evoked by both PGF_2a and Ot, while contractile responses induced by 5-HT were not affected. In the guinea-pig ileum, the HE of H. martiana (50 and 100 μg/ml) caused a discrete rightward displacement of the BK and ACh concentration—response curves. Higher concentrations of the HE of H. martiana (200 μg/mL) caused a marked depression of BK and ACh-induced maximal responses. These findings show that the active principle(s) presents in the HE from the bark of H. martiana exhibits an interesting pharmacological profile against several neurotransmitter-induced contractions in nonvascular smooth muscles. Such actions may be relevant for supporting, at least in part, the use of this plant in folk medicine.     

Analgesic and anti-inflammatory activities of the crude hydroalcoholic extract obtained from the bark of Hymenaea martiana

Experiments were designed to examine the analgesic and anti-inflammatory activities of the crude hydroalcoholic extract (CE) of Hymenaea martiana. The CE of H. martiana (25-200 mg/kg, i.p.) caused a graded inhibition of hindpaw oedema induced by carrageenan, PAF-acether (PAF), serotonin (5-HT), dextran and histamine (HIS). However, the CE given orally up to 500 mg/kg had no effect on the agonist-induced hindpaw oedema. The CE given intraperitoneally, but not orally, caused a graded and pronounced inhibition of His, 5-HT, bradykinin (BK) and PAF-induced increase of vascular permeability. When the CE was given orally (300 mg/kg) once a day for 15 days it caused a significant increase of agonist-induced increase of vascular permeability. The CE given either by p.o. or by i.p. routes (100-800 mg/kg) dose-dependently inhibited arachidonic acid (AA)-induced ear oedema in mice, being significantly more potent when it was given by the latter route. In contrast, CE at the same doses, failed to inhibit croton-oil-induced ear oedema in mice. The CE of H. martiana given by either i.p. or p.o. routes caused a marked and dose-dependent antinociceptive activity as revealed by its antagonistic action against acetylcholine, acetic acid or AA-induced writhing responses in mice, being more effective when given intraperitoneally. These results, and those previously reported with the CE of H. martiana in the isolated preparations, provide strong experimental support which argues in favour of the beneficial use of this plant extract in folk medicine. The exact mechanism that underlies its analgesic and anti-inflammatory profiles remains unclear, but may result from its ability to inhibit the generation of lipoxygenase and/or cyclooxygenase products of the arachidonic acid pathway.     

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.     

Herbal medicine Catuama induces endothelium-dependent and -independent vasorelaxant action on isolated vessels from rats,guinea-pigs and rabbits

The present study was designed to examine the vasorelaxant action of the herbal medicine Catuama and the hydroalcoholic extracts (HE) of each plant present in this product and to compare their effects with that caused by acetylcholine (ACh) in intact (⁺E) or in endothelium-rubbed (⁻E) rings of rat thoracic aorta (RA), guinea-pig pulmonary artery (GPPA), guinea-pig mesenteric artery (GPMA), rabbit pulmonary artery (RPA), rabbit mesenteric artery (RMA) precontracted with noradrenaline (NA) or phenylephrine (PE). The extract of Catuama (1-3000 μg/mL) produced graded relaxation of RA, ⁺E or ⁻E, with mean EC₅₀ of 430 μg/mL and ≊ 3000 μg/mL and E_max of 81 % ± 15 % and 47% ± 4 %, respectively. The nitric oxide (NO) synthase inhibitor, N^ω-nitro-L -arginine (L -NOARG, 100 μM ), inhibited in vasorelaxant action (p < 0.05) in RA (⁺E), while indomethacin (3 μM ), propranolol (1 μM ), glibenclamide (1 μM ), methylene blue (10 μM ) and apamin (0.1 μM ) had no significant effect. ACh (1-1000 μM ) caused graded relaxation in RA with ⁺E, these effects being markedly antagonized by L -NOARG (100 μM ), methylene blue (10 μM ) and partially by apamin (0.1 μM ), but not by indomethacin (3 μM ), glibenclamide (1 μM ) or propranolol (1 μM ). The Catuama extract (1-3000 μg/mL) produces partial relaxations in rings of RMA (mean EC₅₀ of 1073 μg7/ml and E_max of 56 % ± 13 %), an effect which was antagonized by L -NOARG (100 μM ). In RPA (⁺E) the extract produces partial relaxation followed by contraction (E_max 28 % ± 6 %), an effect which was abolished by L -NOARG (100 μM ) or methylene blue (10 μM ). The extract caused graded relaxation in rings of GPPA and GPMA with mean EC₅₀ values of 60 μg/mL and 1148 μg/mL and E_max 96% ± 2% and 88% ± 12%, respectively. L -NOARG (100 μM ) blocked the Catuama extract vasorelaxation in GPPA and only partially in GPMA, but markedly antagonized the vasorelaxations caused by ACh in both GPPA andRMA. The HE Paullinea cupana, Zinziber officinalis and Trichilia catigua (1-3000 μg/mL) caused a graded vasorelaxant effect ⁺E of RA with a mean EC₅₀ of 22, 55 and 1793 μg/mL and E_max 100%, 86% ± 7% 70% ± 2%, respectively. In addition the HE of P. cupana also caused graded relaxation in ⁻E of RA with EC₅₀ and E_max of 233 μg/mL and 100%, respectively, while T. catigua and Z. officinalis produced partial relaxation in RA ⁺E. In contrast the HE of Ptychopetalum olacoides caused little contraction (46% ± 14%). These results demonstrate that the medicinal herb Catuama produces significant vasorelaxation responses in vessels from different animal species, and show that its effects are in great part dependent on the release of NO or NO-derived substances. Our results also demonstrate that the vasorelaxant action of the product Catuama seems to be due to the action of the active principles present mainly in P. cupana; T. catigua and, to a lesser extent, in Z. officinalis. Such results may contribute to the explanation of its beneficial effect of Catuama herbal medicine in the management of cardiovascular disturbances. © 1997 John Wiley & Sons, Ltd.     

吴茱萸对家兔离体胸主动脉作用机制的实验研究

 目的 观察贵州余庆种植的吴茱萸对家兔离体胸主动脉的作用,探讨其可能的作用机制。方法 取家兔离体胸主动脉条,分为内皮完整组和去内皮组,观察累积质量浓度的吴茱萸水煎液对胸主动脉条的作用。同时用左旋硝基精氨酸甲酯、吲哚美辛苦及BaCl₂预孵育血管环,观察吴茱萸的作用。结果 贵州余庆种植的吴茱萸水煎液能够浓度依赖性地提高血管环张力,且对内皮完整血管环的收缩作用明显强于去内皮血管环。用左旋硝基精氨酸甲酯和吲哚美辛苦预孵育血管环后,吴茱萸使血管环张力上升的幅度降低;用BaCl₂预孵育血管环后对吴茱萸的缩血管作用没有影响。 结论 贵州余庆种植的吴茱萸水煎液对家兔离体胸主动脉有内皮依赖性的收缩作用,同时推测吴茱萸水煎液内还存在可诱导血管内皮细胞释放NO和前列环素的成分,使血管舒张,部分抵消其收缩作用。     

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.     

The source of ca2+ for the spasmolytic actions of longicaudatine,a bisindole alkaloid isolated from Strychnos trinervis (Vell.) Mart. (Loganiaceae)

Longicaudatine, a tertiary bisindole alkaloid isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), antagonized in a noncompetitive manner, carbachol and histamine induced contractions of the guinea-pig ileum and bradykinin responses in the rat uterus. The respective pD₂' values (mean ± SE) were 4.61 ± 0.21, 4.98 ± 0.04 and 4.49 ± 0.01. Longicaudatine, unlike verapamil, had no effect on voltage dependent Ca²⁺ channels, as it failed to inhibit KCI or CaCl₂ induced contractions of guinea-pig ileum and depolarized rat uterus respectively. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, longicaudatine produced a slower and weaker inhibition of noradrenaline induced sustained contractions of rabbit aortic strips. However, in the aorta, the alkaloid antagonized the intracellular calcium dependent transient contractions of noradrenaline and longicaudatine (IC₅₀, 5.01 × 10^?7 M) was approximately 133 times more potent that procaine (IC₅₀, 6.68 × 10^?5 M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Longicaudatine may exert nonspecific spasmolytic effects by acting on intracellular Ca²⁺ stores, rather than on depolarization dependent or receptor operated Ca²⁺ channels.     

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。     

Pharmacological mechanisms involved in the vasodilator effects of extracts from Echinodorus grandiflorus

We investigated the vascular effects of a crude aqueous extract (AEEG) of Echinodorus grandiflorus (Alismataceae) using the in vitro experimental models of the rabbit isolated aorta and perfused kidney. Echinodorus grandiflorus, a native semi-aquatic plant widely distributed in Brazil, has been extensively used in Brazilian folk medicine for the treatment of high blood pressure and inflammatory diseases. The bolus injection of AEEG (0.1-10 mg) into the rabbit renal circulation pre-contracted with norepinephrine induced marked and dose-dependent vasodilator responses (maximum of 37+/-4%; n=6; P<0.001), which was similar to that induced by injection of 10 mmol acetylcholine (41+/-3%). Moreover, AEEG elicited a significant and concentration-dependent relaxation in the endothelium-intact, but not endothelium-denuded aortic rings, reaching the maximum of 81+/-5% (n=7, P<0.001). Inhibition of the nitric oxide-cGMP pathway with L-NAME (100 microM) or Methylene Blue (20 microM) reduced maximum relaxation induced by AEEG from 81+/-5% to 46+/-3 and 45+/-3%, respectively (n=7, P<0.001). A similar reduction was obtained with the incubation of the aortic rings with the selective PAF receptor antagonist WEB 2086 (10 microM) (from 81+/-5% to 55+/-3%; n=7; P<0.01). Conversely, blockade of muscarinic receptors with atropine (10 microM) did not affect the vasodilator effects of AEEG, while inhibition of the enzyme cyclooxigenase not only did not block, but rather potentiated vasodilation induced by AEEG (n=7, P<0.001). Finally, blockade of Ca(2+)- and ATP-activated K(+) channels using the specific blockers charydbotoxin (100 nM) and glibenclamide (3 microM), respectively, did not modify aortic relaxation induced by AEEG. We conclude that water-soluble extracts from leaves of Echinodorus grandiflorus elicit an endothelium-dependent, nitric oxide and PAF receptor-mediated vasodilation in rabbit aortic rings, which does not appear to involve the generation of vasodilating prostaglandins or the activation of K(+) channels. This potent vasodilator effect of the extracts was confirmed in the isolated rabbit renal circulation.     

The Lignan (‐)‐Cubebin Inhibits Vascular Contraction and Induces Relaxation Via Nitric Oxide Activation in Isolated Rat Aorta

Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti‐inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (‐)‐cubebin in isolated rat aortic rings pre‐contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium‐dependent relaxation was evoked by acetylcholine and (‐)‐cubebin in intact aortic rings, while endothelium‐independent vasorelaxation was elicited by sodium nitroprusside and (‐)‐cubebin in denuded rings. Cumulative concentration–response curves for Phe (10^?10–10^?5 M) were determined for endothelium‐intact and endothelium‐denuded aortic rings in either the presence or absence of (‐)‐cubebin. Dose–response curves were also constructed for pre‐incubation of vascular rings with Nω‐nitro‐L‐arginine methyl ester (L‐NAME) (a non‐specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H‐[1,2,4] oxadiazolo [4,3‐a]quinoxalin‐1‐one (ODQ) (a guanylyl cyclase inhibitor). (‐)‐Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L‐NAME and ODQ, but not with indomethacin. In addition, (‐)‐cubebin was able to reduce Phe contraction in the case of intact rings. These results suggest that (‐)‐cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of phenylpropanoid and iridoid glycosides on free radical-induced impairment of endothelium-dependent relaxation in rat aortic rings.

The protective effect of phenylpropanoid glycosides, forsythoside B and alyssonoside, and the iridoid glycoside lamiide, isolated from the aerial parts of Phlomis pungens var. pungens, against free radical-induced impairment of endothelium-dependent relaxation in isolated rat aorta was investigated. Aortic rings were exposed to free radicals by the electrolysis of the physiological bathing solution. Free radical-induced inhibition of the endothelium-dependent relaxation in response to acetylcholine was countered by incubation of the aortic rings before electrolysis with the aqueous extract (200 microg/ml), phenylpropanoid fraction (100 microg/ml) and iridoid fraction (150 microg/ml) of P. pungens var. pungens. Major components of the phenylpropanoid fraction forsythoside B and alyssonoside also prevented the inhibition of the acetylcholine response, at 10(-4) M concentration. However, the major component of iridoid fraction lamiide was found ineffective at the same concentration. The protective activity of phenylpropanoid glycosides against the free radical-induced impairment of endothelium-dependent relaxation may be related to their free radical scavenging property.     

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.     

Pharmacological studies on hypotensive and spasmolytic activities of pure compounds from Moringa oleifera

Bioassay directed fractionation of an ethanolic extract of Moringa oleifera (MO) leaves resulted in the isolation of four pure compounds, niazinin A (1), niazinin B (2), niazimicin (3) and niaziminin A + B (4 + 5). Intravenous administration of either one of the compounds (1–10 mg/kg) produced hypotensive and bradycardiac effects in anaesthetized rats. Pretreatment of the animals with atropine (1 mg/kg) completely abolished the hypotensive and bradycardiac effects of acetylcholine (ACh), whereas cardiovascular responses to the test compounds remained unaltered, ruling out the possible involvement of muscarinic receptor activation. In isolated guinea-pig atria all the compounds (50–150 μg/mL) produced negative inotropic and chronotropic effects. Each compound inhibited K⁺ -induced contractions in rabbit aorta as well as ileal contractions induced by ACh or histamine at similar concentrations. Spontaneous contractions of rat uterus were also inhibited equally by all compounds. These data indicate that the direct depressant action of these compounds exhibited on all the isolated preparations tested is probably responsible for its hypotensive and bradycardiac effects observed in vivo. Moreover, spasmolytic activity exhibited by the constituents of the plant provides a scientific basis for the traditional uses of the plant in gastrointestinal motility disorders.     

Nitric oxide-dependent vasodilatation by ethanolic extract of Hancornia speciosa via phosphatidyl-inositol 3-kinase

The vasodilator effect of the ethanolic extract of leaves from Hancornia speciosa Gomes (HSE) was studied in rat aortic rings. HSE produced a concentration-dependent vasodilatation (pIC(50)=5.6+/-0.1), which was completely abolished in endothelium-denuded vessels. The endothelium-dependent vasodilatation induced by HSE was abolished by l-NAME (100 microM), a nitric oxide (NO) synthase inhibitor, but not atropine (1 microM; pIC(50)=5.6+/-0.2), a muscarinic receptor antagonist, nor indomethacin (10 microM; pIC(50)=5.4+/-0.2), a cyclooxygenase inhibitor. The concentration-response curve of HSE was significantly shifted to the left by superoxide dismutase (SOD; 300U/mL). In addition, while SOD displaced the 3-morpholino-sidnonimine (SIN-1; P<0.05) concentration-effect curve to the left, HSE (50 microg/mL) had no effect. Finally, wortmannin (0.3 microM), an inhibitor of phosphatidyl-inositol 3-kinase (PI3K), dramatically reduced the vasodilator effect of HSE. Together, these findings lead us to conclude that HSE induces a NO- and endothelium-dependent vasodilatation in rat aortic preparations, likely by a mechanism dependent on the activation of PI3K.     

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.     

Beneficial effect of aqueous garlic extract on the vascular reactivity of streptozotocin-diabetic rats

The present study evaluated the beneficial effect of aqueous extract of garlic (Allium sativum L.; 100mg/kg/day) on the alterations in vascular reactivity of streptozotocin-diabetic rats. After 8 weeks of treatment, thoracic aortic rings of rats were mounted in organ baths and contractile responses to phenylephrine and relaxant responses to acetylcholine and isosorbide dinitrate were assessed. Induction of diabetes significantly increased contractile responses to phenylephrine and impaired endothelium-dependent relaxations to acetylcholine in aortic rings, but did not change endothelium-independent relaxation to isosorbide dinitrate. Garlic administration significantly improved the impaired endothelium-dependent relaxations and decreased the enhanced contractile response to phenylephrine in diabetic rats. It is concluded that intraperitoneal administration of aqueous garlic extract can improve endothelial dysfunction in insulin-dependent model of uncontrolled diabetes.     

Analysis of the mechanisms underlying the vasorelaxant action of coptisine in rat aortic rings

The aim of the present study was to evaluate the vasorelaxant effects of coptisine and its possible mechanisms in isolated rat aortic rings. Coptisine was evaluated on isolated rat aortic rings precontracted with norepinephrine (NE) and KCl. The mechanisms were evaluated in the presence or absence of specific pharmacological inhibitors. Coptisine (1 ~ 200 μM) relaxed NE (1 μM) or KCl (60 mM) induced sustained contraction with pEC(50) values of 4.49 ± 0.48 and 4.85 ± 0.57 in a concentration dependent manner. Pretreatment with coptisine (10, 50 or 100 μM) also inhibited concentration-response curves to NE and KCl. The vasorelaxant effect of coptisine was attenuated significantly by endothelium removal, and incubation with Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM), methylene blue (10 μM) and indomethacin (5 μM) partially reduced the vasorelaxant effect of coptisine. In endothelium-denuded rings, the vasorelaxant effect of coptisine was reduced significantly by 4-aminopyridine (4-AP, 100 μM), but not glibenclamide (10 μM) ortetraethylammonium (TEA, 5 mM). Coptisine also reduced NE-induced transient contraction in Ca(2+)-free solution, and inhibited contraction induced by increasing external calcium in Ca(2+)-free medium plus 60 mM KCl. It was concluded that coptisine induced both endothelium-dependent and -independent relaxation in rat aortic rings. The NO-cGMP mediated pathway may be involved in the endothelium-dependent relaxation and in the activation of voltage-dependent K(+) channels, contributing in part to the endothelium-independent relaxation bycoptisine. Coptisine also blocks extracellular Ca(2+) influx by interacting with both voltage- and receptor-operated Ca(2+) channels.     

螺旋藻多糖和鼠尾藻多糖对四氧嘧啶致糖尿病大鼠血管的保护作用

目的研究螺旋藻粗提多糖和鼠尾藻粗提多糖联合使用对四氧嘧啶糖尿病大鼠血管的保护作用。方法2种多糖以1∶1混合,分别以123,368,1103mg·kg^-1灌胃给予四氧嘧啶致高血糖大鼠高、中、低各组。连续给药6周后,分别测定各组大鼠的血糖、TC,HDLC,TG,NO,ET。并取各鼠胸主动脉测定其对去甲肾上腺素(NE)和乙酰胆碱(ACh)舒缩反应的变化。结果混合多糖能降低ALX性糖尿病大鼠的血糖与血清TC,TG,NO,ET,升高血清HDLC。ALX模型大鼠主动脉对NE的收缩反应显著增强,对ACh舒张反应显著减弱。混合多糖能显著降低NE的收缩反应,改善糖尿病大鼠血管内皮依赖的舒缩反应功能。结论2种多糖联合使用能降低血糖并对血管有一定的保护作用。     

半夏白术天麻汤水提取物对大鼠离体胸主动脉环的舒张作用及机制

目的：观察半夏白术天麻汤水提取物对血管功能的影响并探讨其作用机制。方法：记录苯肾上腺素（PE）和KCl预收缩的离体大鼠胸主动脉环张力变化,观察半夏白术天麻汤水提取物舒血管作用及不同工具药对舒血管作用的影响。结果：半夏白术天麻汤水提取物（0．5,0．8,1．0mg／ml）对PE（1．0μmol·L^-1）预收缩的大鼠主动脉环均有内皮依赖的、浓度依赖性的舒张作用。但对KCl（50mmol·L^-1）和鸟苷酸环化酶抑制剂亚甲蓝（MB）（10μmol·L^-1）可抑制半夏白术天麻汤水提取物诱导的血管舒张作用。结论：半夏白术天麻汤水提取物具有内皮依赖性的舒张血管作用,此作用主要通过NO-cGMP途径。     

山楂水提取物对正常大鼠离体胸主动脉环的舒张作用及其机制

目的：探讨山楂水提取物对胸主动脉环的舒张作用及其作用机制。方法：采用累积加药法,检测山楂水提取物（0．1,0．3和0．5mg／m1）对苯肾上腺素（PE）1．0μmol．L^-1和KCl50mmol．L^-1预收缩的胸主动脉环张力的影响。结果：山植水提取物对离体大鼠内皮完整和去内皮的胸主动脉环均有浓度依赖性的舒张作用,而对苯肾上腺素（PE）预收缩血管的舒张作用是内皮依赖性的。用一氧化氮合酶抑制剂L-NAME和鸟苷酸环化酶抑制剂MB预处理后,两者的血管舒张作用均被阻断。但用环氧合酶抑制剂吲哚关辛,不能阻断山楂引起的舒张血管作用。结论：山楂水提取物可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。