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.     

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.     

Vasorelaxant effect of the aqueous extract of Ajuga iva in rat aorta

The aim of the present study was to investigate the ex vivo and in vitro vascular activity of the aqueous extract of Ajuga iva (L.) Schreber (Labiatae) in normotensive Wistar rats. Chronic oral administration of the extract of Ajuga iva did not significantly affect the systolic blood pressure. In aorta isolated from Ajuga iva-treated rats, the contractile response to noradrenaline was depressed compared to the responses obtained in aorta from untreated rats but the endothelium-dependent relaxation evoked by acetylcholine was not affected. In vitro, Ajuga iva extract inhibited the contraction evoked by noradrenaline. The addition of Ajuga iva extract during the plateau phase of noradrenaline-evoked contraction produced a relaxation that was sensitive to N-nitro-L-arginine. After pre-incubation of the artery in the presence of the plant extract, vasorelaxant effect was markedly less pronounced. The endothelium-dependent relaxation induced by acetylcholine was concentration-dependently blunted in the presence of Ajuga iva extract in the bathing solution. This study indicates that the aqueous extract of Ajuga iva possesses NO-mediated and NO-independent vasorelaxing properties in vitro while only the endothelium-independent effect was observed ex vivo.     

Chronic Administration of Daidzein,a Soybean Isoflavone,Improves Endothelial Dysfunction and Attenuates Oxidative Stress in Streptozotocin‐induced Diabetic Rats

The effect of chronic daidzein, a soybean isoflavone, on aortic reactivity of streptozotocin‐diabetic rats was studied. Male diabetic rats received daidzein for 7 weeks a week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Maximum contractile response of endothelium‐intact rings to PE was significantly lower in daidzein‐treated diabetic rats relative to untreated diabetic rats, and endothelium removal abolished this difference. Endothelium‐dependent relaxation to ACh was significantly higher in daidzein‐treated diabetic rats as compared with diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor N(G)‐nitro‐l‐arginine methyl ester and/or indomethacin attenuated it. Two‐month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity, and daidzein treatment significantly reversed the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with daidzein could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and prostaglandin‐related pathways, and via attenuation of oxidative stress in aortic tissue and endothelium integrity seems essential for this effect. Copyright © 2012 John Wiley & Sons, Ltd.     

A pharmacological study on Berberis vulgaris fruit extract

Berberis vulgaris fruit (barberry) is known for its antiarrhythmic and sedative effects in Iranian traditional medicine. The effects of crude aqueous extract of barberry on rat arterial blood pressure and the contractile responses of isolated rat aortic rings and mesenteric bed to phenylephrine were investigated. We also examined effect of the extract on potassium currents recorded from cells in parabrachial nucleus and cerebellum rejoins of rat brain. Administration of the extract (0.05-1 mg/100 g body weight of rat) significantly reduced the mean arterial blood pressure and heart rate in anaesthetized normotensive and desoxycorticosteron acetate-induced hypertensive rats in a dose-dependent manner. Concentration-response curves for phenylephrine effects on isolated rat aortic rings and the isolated mesenteric beds in the presence of the extract were significantly shifted to the right. Application of the extract (1-50 microg/ml) shifted the activation threshold voltage to more negative potentials, leading to an enhancement in magnitude of the outward potassium current recorded from cells present in rat brain slices of parabrachial nucleus and cerebellum. This effect on potassium current may explain the sedative and neuroprotective effects of barberry. The present data support the hypothesis that the aqueous extract of barberry has beneficial effects on both cardiovascular and neural system suggesting a potential use for treatment of hypertension, tachycardia and some neuronal disorders, such as epilepsy and convulsion.     

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.     

Effects of Kaempferia parviflora Wall. Ex Baker on endothelial dysfunction in streptozotocin-induced diabetic rats

Aim of the study

The aim of the present study was to investigate an ethanolic extract of Kaempferia parviflora (KPE) reduces oxidative stress and preserves endothelial function in aortae from diabetic rats.

Materials and methods

Diabetes was induced in Sprague-Dawley rats by streptozotocin (STZ) treatment (55 mg/kg i.v.). Vascular reactivity and superoxide generation were assessed in aortic rings using standard organ bath techniques and lucigenin-enhanced chemiluminescence, respectively.

Results

Eight weeks after STZ treatment blood glucose was elevated compared to citrate treated control rats and there was an increased aortic generation of superoxide anion. In aortic rings acetylcholine-induced relaxation was impaired whereas endothelium-independent relaxation to sodium nitroprusside was unaffected. When aortic rings were acutely exposed to KPE (1, 10 and 100 μg/ml) there was a significant reduction in the detection of superoxide anion and enhanced relaxation to acetylcholine. Two separate groups of rats (control and diabetic) were orally administered daily with KPE (100 mg/kg body weight) for 4 weeks. KPE treatment reduced superoxide generation and increased the nitrite levels in diabetic aortae, and enhanced acetylcholine-induced relaxation. In the presence of N^G-nitro-l-arginine (l-NNA), the relaxation to acetylcholine in aortic rings of diabetic rats was only partially inhibited, but was totally abolished in aortic rings from the KPE-treated diabetic rats. Indomethacin did not affect relaxation to acetylcholine in aortic rings of any group.

Conclusions

These results suggest that KPE, acutely in vitro or after 4 weeks administration in vivo, reduces oxidant stress, increases NO bioavailability and preserves endothelium-dependent relaxation in aortae from diabetic rats.     

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.     

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.     

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。