Hymenaea rubriflora Ducke stem bark extract has vasorelaxant and contractile inhibition capacity

Abstract We investigated the vasodilatory effects of Hymenaea rubriflora Ducke stem bark extract (HR- HAc). Vascular reactivity of the aortic rings of Wistar rats was tested by in vitro cumulative doses (0.1 - 729 μg/mL). Rats (n=5) were treated with 25 (G25), 50 (G50) and 100 (G100) mg/ kg of HR-HAc or saline (control group - CG) for four weeks. An in vitro assay resulted in dose-dependent relaxation of the aortic rings with functional endothelium, which was inhibited in the presence of L-NAME. Rings of the treated animals increased acetylcholine relaxing potency at all doses, with a greater effect on G50 (pD2 = 7.8±0.1, Emax = 95.6±1.1) and a decreased contractile potency to phenylephrine in G25 (pD2 = 6.9±0.06, Emax = 61.5±6.0%) and G50 (pD2= 6.6±0.06, Emax = 71.0±8.5%) when compared to the CG in the presence and absence of endothelium (pD2= 6.4± 0.1, 6.4±0.1 and 6.9±0.1, respectively). Cumulative doses of nitroprusside resulted in increased relaxing potency in all treated groups and maintained Emax at 100%. It is concluded that HR-HAc has vasorelaxant capacity and inhibitory vascular contraction activity applied either directly to aortic rings or after treatment with in vivo supplementation, which places this extract as a potential nutraceutical or pharmacological agent for treating diseases associated with vascular dysfunction.

Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome

Metabolic syndrome is a multifaceted condition associated with a greater risk of various disorders (e.g., diabetes and heart disease). In a rat model of metabolic syndrome, an acute in vitro application of rosuvastatin causes relaxation of aortic rings. Since the outcome of a subchronic rosuvastatin treatment is unknown, the present study explored its effect on acetylcholine-induced vasorelaxation of aortic rings from rats with metabolic syndrome. Animals were submitted to a 16-week treatment, including a standard diet, a cafeteria-style diet (CAF-diet), or a CAF-diet with daily rosuvastatin treatment (10 mg/kg). After confirming the development of metabolic syndrome in rats, aortic segments were extracted from these animals (those treated with rosuvastatin and untreated) and the acetylcholine-induced relaxant effect on the corresponding rings was evaluated. Concentration-response curves were constructed for this effect in the presence/absence of L-NAME, ODQ, KT 5823, 4-aminopyridine (4-AP), tetraethylammonium (TEA), apamin plus charybdotoxin, glibenclamide, indomethacin, clotrimazole, and cycloheximide pretreatment. Compared to rings from control rats, acetylcholine-induced vasorelaxation decreased in rings from animals with metabolic syndrome, and was maintained at a normal level in animals with metabolic syndrome plus rosuvastatin treatment. The effect of rosuvastatin was inhibited by L-NAME, ODQ, KT 5823, TEA, apamin plus charybdotoxin, but unaffected by 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. In conclusion, the subchronic administration of rosuvastatin to rats with metabolic syndrome improved the acetylcholine-induced relaxant response, involving stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

Mechanisms underlying the vascular relaxation activities of Zingiber officinale var. rubrum in thoracic aorta of spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To evaluate vasorelaxant and vasoconstriction effects of Zingiber officinale var. rubrum (ZOVR) on live rats and isolated aortic rings of spontaneously hypertensive rats (SHRs).@*METHODS@#Extracts of ZOVR were subjected to in-vivo antihypertensive screening using noninvasive blood pressures in SHRs. The most potent extract, ZOVR petroleum ether extract (ZOP) was then fractionated using n-hexane, chloroform and water. Isolated thoracic aortic rings were harvested and subjected to vascular relaxation studies of n-hexane fraction of ZOP (HFZOP) with incubation of different antagonists such as N-nitro-l-arginine methyl ester (L-NAME, 10 µmol/L), indomethacin (10 µmol/L), methylene blue (10 µmol/L), atropine (1 µmol/L), glibenclamide (10 µmol/L), prazosin (0.01 µmol/L), and propranolol (1 µmol/L).@*RESULTS@#During the screening of various ZOVR extracts, ZOP produced the most reduction in blood pressures of SHRs and so did HFZOP. HFZOP significantly decreased phenylephrine-induced contraction and enhanced acetylcholine-induced relaxation. L-NAME, indomethacin, methylene blue, atropine, and glibenclamide significantly potentiated the vasorelaxant effects of HFZOP. Propranolol and prazosin did not alter the vasorelaxant effects of HFZOP. HFZOP significantly suppressed the Ca-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca-free medium.@*CONCLUSION@#This study demonstrates that ZOP may exert an antihypertensive effect in the SHR model. Its possible vascular relaxation mechanisms involve nitric oxide and prostacyclin release, activation of cGMP-K channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca release from intracellular stores. Possible active compounds that contribute to the vasorelaxant effects are 6-gingerol, 8-gingerol and 6-shogaol.

Chenopodium ambrosioides induces an endothelium-dependent relaxation of rat isolated aorta / 中西医结合学报

OBJECTIVE@#This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioides on the isolated rat aorta, and to explore its mechanism of action.@*METHODS@#The vasorelaxant effect and the mode of action of various extracts from the leaves of C. ambrosioides were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, ethyl acetate and methanol fractions were analyzed, using thin-layer chromatography and high-performance liquid chromatography techniques, for their polyphenolic content.@*RESULTS@#The various active extracts of C. ambrosioides at four concentrations (10, 10, 10 and 1 mg/mL) relaxed the contraction elicited by phenylephrine, in a concentration-dependent manner. This effect seems to be endothelium-dependent, since the vasodilatory effect was entirely absent in denuded aortic rings. The vasorelaxant effect of the methanol fraction (MF) of C. ambrosioides at 1 mg/mL was also inhibited by atropine and tetraethylammonium. This effect remained unchanged by Nω-nitro-l-arginine methyl ester hydrochloride and glibenclamide. The preliminary phytochemical analysis showed that the leaves of C. ambrosioides are rich in phenolic and flavonoid derivatives.@*CONCLUSION@#These results suggest that the MF of C. ambrosioides produces an endothelium-dependent relaxation of the isolated rat aorta, which is thought to be mediated mainly through stimulation of the muscarinic receptors, and probably involving the opening of Ca-activated potassium channels.

Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05) by 10-5 M L-NAME (a direct inhibitor of nitric oxide synthase), 10-7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase), 10-6 M KT 5823 (an inhibitor of protein kinase G), 10-2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker) and 10-7 M apamin plus 10-7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively), and was blocked by 8×10-2 M potassium (a high concentration) and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

Relaxation effect of buddleoside combined with luteolin on isolated vessels in vivo and its mechanism / 中国中药杂志

To study the relaxation effect of buddleoside combined with luteolin on aortic rings in SD rats and its mechanism. The effect of buddleoside alone(7.5×10⁻⁶g•mL⁻¹), luteolin alone(7.5×10⁻⁶g•mL⁻¹) and the combination of buddleoside and luteolin(1∶4) on norepinephrine-induced contractility of complete, endothelium-denuded, and L-NAME and indomethacin-pretreated thoracic aorta in SD rats were observed in the in vitro ring tension test. Western blot was used to detect p-Akt and p-eNOS protein expressions in the thoracic aorta. The experimental results showed that buddleoside combined with luteolin could significantly increase the relaxation rate of blood vessels and endothelium and L-NAME-pretreated vascular rings compared with the two single administrations. And buddleoside combined with luteolin could also significantly increase p-Akt and p-eNOS protein expressions.The results suggested that the combination of buddleoside and luteolin could effectively relax the blood vessel, and the mechanism may be to increase the synthesis and release of NO and reach the role of relaxing blood vessel by activating PI3K/Akt/NO signaling pathway and enhancing the activity of eNOS.

Arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells: comparison of vasorelaxant effects of verapamil and phentolamine

Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K(KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.

Mitochondrial uncoupler triclosan induces vasorelaxation of rat arteries

Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca], mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine (PE)- and high K(KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE- and KPSS-induced constriction. Triclosan induces vasorelaxation without involving Kchannel activation in smooth muscle cells of arteries. Triclosan treatment increased cytosolic [Ca], mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively.

Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.

Effects of CaSR on vascular relaxation/constriction in rats / 局解手术学杂志

Objective To investigate the effects of calcium sensing receptor (CaSR)on vasorelaxation/vasoconstriction of superior mes-enteric artery (SMA)in rats and its relationship to endothelium.Methods With endothelium-intact and endothelium-denuded SMA rings of rats,the effects of CaSR-specific allosteric modulator cinacalcet on the SMA rings pre-contracted with norepinephrine (NE),and vascular contractile response /relaxation reactivity were observed.Results Cinacalcet had no effects on resting tension of SMA rings with or without endothelium.Cinacalcet caused a significant relaxation in the endothelium-intact SMA rings pre-contraction with NE in a dose-dependent manner.Endothelium denudation abolished cinacalcet-induced vasorelaxation.Pretreatment with cinacalcet for 30 minutes decreased the con-tractile response of endothelium-intact SMA rings to NE,but had no significant influence on relaxation reactivity.In the endothelium-denuded SMA rings,cinacalcet did not affect both vasoconstriction and vasorelaxation.Conclusion CaSR plays an important role in the regulation of the vascular reactivity,and this effect is endothelium-dependent.

Role of Kv7 Channels in Vascular Dysfunction associated with Metabolic Syndrome

Vasoconstriction is regulated by various ion channels expressed in the plasma membrane of vascular smooth muscle cells. In particular, potassium (K+) channel activity determines resting membrane potential and regulates intracellular calcium (Ca2+) signaling. A number of studies have suggested that dysregulation of K+ channel activity is associated with increased myogenic tone or diminished vasorelaxation. Among the various families of K+ channels, voltage-dependent K+ channels (Kv channels) encoded by the KCNQ gene family (Kv7 channels or M channels) are widely expressed in various blood vessels isolated from mouse, rat, and human. Recent studies have demonstrated that a subunit of the Kv7 channel, Kv7.4, is down-regulated in the aorta and mesenteric and renal arteries of the Spontaneously Hypertensive Rat (SHR) model. Previous studies have also suggested that Kv7 channels play an important role in the regulation of vasorelaxation/vasoconstriction in response to activators/blockers. In addition, previous studies have indicated that hypertension, diabetes mellitus, and cerebrovascular disease result in development of vascular dysfunction associated with Kv7 abnormalities in various animal models. This review focuses on the potential role of the Kv7 channel in vascular dysfunction.

Mechanism of hyperoside-induced dilatation in middle cerebral arteries of rats subjected to cerebral ischemia reperfusion / 中国药学杂志

OBJECTIVE: To investigate the dilatation and mechanism of hyperoside (Hyp) in middle cerebral arteries (MCA) of rats subjected to cerebral ischemia reperfusion (CIR). METHODS: Rat isolated MCA segments were used for surveying vasomotoricity in a pressurized chamber. Transmembrane potential was recorded by using glass microelectrodes to evaluate MCA vascular smooth muscle cell hyperpolarization. (1×10-6-1×10-4) mol·L-1 Hyp was used to investigate the effects on vasodilatation and hyperpolariza-tion in MCA of rats subjected to CIR. And the effects of nitric oxide synthase inhibitor (N-nitro-L-arginine-methyl-ester, L-NAME, 3×10-5 mol·L-1) or L-NAME plus prostaglandin I2 synthetase inhibitor (indomethacin, Indo, 1×10-5 mol·L-1) on vasorelaxation and hyperpolarization induced by Hyp were observed, respectively. Auto ELISA Detector and nitrate reductase methods were utilized to detect the H2 S and NO content in the cerebrum of rats. RESULTS: Hyp remarkably induced dose-dependent vasodilatation and hyperpolarization in 1×10-7 mol·L-1 U46619-preconstricted MCA of CIR rats. Hyp-mediated effects were notably attenuated after removal of endothelium in CIR MCA as compared with endothelium-intact group (P-5 mol·L-1) plus Indo (1×10-5 mol·L-1), the vasodilatation and hyperpolarization evoked by Hyp were significantly attenuated in sham operation group and CIR MCAs. Compared with the residual effects in sham vessels, those of CIR MCAs were remarkably potentiated (P-3 mol·L-1), an inhibitor of Ca2+-activated potassium channel, or PPG (1×10-4 mol·L-1), an inhibitor of the endogenous H2S synthese-CSE could markedly restrain Hyp-induced non-NO and non-PGP relaxation and hyperpolarization in sham and CIR vessels. As compared with CIR group, pretreatment with Hyp increased the H2S contents while decreased the NO contents. CONCLUSION: Hyp has the potential to evoke endothelium-dependent and endothelium-inde pendent effects in CIR MCAs. In these responses to Hyp, NO-mediated response is downregulated while endothelium-derived hyperpolarizing factor (EDHF) is upregulated, ie, endogenous H2S, is upregulated. Hyp can also protect the brain against cerebral ischemia injury by promoting H2S contents and decreasing NO contents of brain tissues.

Vasorelaxation effect of gastrodin on isolated thoracic aorta rings of rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of gastrodin on isolated thoracic aorta rings of rats and to investigate the potential mechanism.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>Compared 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%).</p><p><b>CONCLUSIONS</b>Gastrodin 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.</p>

Effect of hydrogen sulfide on vasorelaxation and content of guanosine 3', 5'-cyclic phosphate in vascular tissue of rats / 中华实用儿科临床杂志

Obgective To observe the effect of hydrogen sulfide (H2S) on vasorelaxation and expression of guanosine 3',5'-cyclic phosphate (cGMP) and activity of cyclic nucleotide phosphodiesterase (PDE) in vascular tissue.Methods H2S donor was provided by sodium bisulfide sodium hydrosulfide.The isolated perfused rat thoracic aorta rings were used to test the relaxation responses to H2S,which recorded by Power Lab system,and the enzyme linked immuno assay was used to detect intracellular cGMP.The activity of PDE was evaluated by using cyclic nucleotide PDE assay kit.Results (1) H2S relaxed the thoracic aorta rings,and the half maximal effective concentration (EC50) for the H2 S relaxation curve,represented by the corresponding concentration of H2 S that achieved 50％ of the maximum relaxation effect,was (1.79 ± 0.31) × 10-5 mol/L.(2)The cGMP content in vascular tissue increased from (22.29 ± 1.59) pmol/L to(41.45 ± 7.49) pmol/L and (31.35 ± 2.56) pmol/L after incubation with 50 μmol/L and 300 μmol/L H2 S,respectively (t =-3.09,t =-2.88;all P ＜ 0.05,n =7-8).(3) cGMP could be lysed into 5'-guanylicacid(5'-GMP) by PDE,which was an important pathway for cGMP degradation.This study showed that PDE activity was decreased in vascular tissue,the 5'-GMP decreased from (0.52 ±0.06) mol/L to (0.25 ±0.06) mol/Land (0.27 ±0.07) mol/L after incubation with 50 μmol/L and 300 μ mol/L H2S,respectively (t =3.21,t =2.58;all P ＜ 0.05,n =7-8).Conclusion The vasorelaxant effects of H2 S might be related to the inhibited activity of PDE and elevated content of cGMP.

Avaliação dos efeitos da ropivacaína sobre a reatividade vascular em artéria mesentérica de rato / Assessment of the effects of ropivacaine on vascular reactivity in rat mesenteric artery

Introdução: A ropivacaína (ROPI) é um anestésico local de longa duração de ação, introduzido mais recentemente em Medicina, mas ainda não disponível para uso odontológico em tubetes. Estudos clínicos e com animais confirmam que a ROPI é um anestésico local eficaz e que possui um efeito vasoconstritor intrínseco. Objetivo: Avaliar os efeitos da ROPI sobre a reatividade vascular em artéria mesentérica isolada de rato, além de comparar esse efeito ao da lidocaína (LIDO) e avaliar o possível envolvimento do endotélio vascular na resposta induzida pela ROPI em anel de artéria mesentérica isolada de rato. Material e Método: Foram utilizados 14 ratos Wistar machos (250-300g). Os animais foram eutanasiados e, através de uma incisão no abdome do animal, foi retirada a artéria mesentérica. Desta artéria, foram obtidos anéis (1-2 mm), que foram mantidos em cubas contendo 10 mL de solução nutritiva de Tyrode mantida a 37 °C e gaseificada com carbogênio. Para o registro das contrações isométricas, cada anel foi suspenso, por linhas de algodão, a um transdutor de força conectado a um sistema de aquisição. RESULTADO: Tanto a LIDO como a ROPI não apresentaram efeito vasoconstritor sobre o tônus basal de anéis com endotélio funcional. Porém, quando os anéis foram pré-contraídos com fenilefrina, ambas as drogas foram capazes de induzir vasorrelaxamentos dependentes da concentração (Emáx = 31,7 ± 3,3%; n = 6, para a LIDO; Emáx = 69 ± 8%; n = 6, para a ROPI), que não foram alterados após a remoção do endotélio (Emáx = 28,7 ± 1,3%; n = 7, para a LIDO; Emáx = 58,8 ± 5,9%; n = 6, para a ROPI). Em anéis sem endotélio ...

Introduction: Ropivacaine (ROPI) is a local anesthetic of long duration of action, more recently introduced in medicine, however is not available for dental use in tubes yet. Clinical and animal studies have confirmed that bupivacaine is an effective anesthetic that also has an intrinsic vasoconstrictor effect. Objective: To evaluate the effects of ropivacaine on vascular reactivity in isolated rat mesenteric artery, compare this to the effect of lidocaine (LIDO) and evaluate the possible involvement of the vascular endothelium induced by ROPI in isolated rat mesenteric artery ring response. Material and Method: It was used 12 male Wistar rats (250-300g). The animals were euthanized and through an incision in the abdomen of the animal, the mesenteric artery was removed. Artery rings (1-2 mm) were obtained by the mesenteric artery, which were kept in vats containing 10 ml of Tyrode's nutrient solution kept at 37 °C and gassed with carbogen. For the recording of isometric contractions, each ring was suspended by cotton lines to a force transducer connected to a data acquisition system. RESULT: Both the LIDO as ROPI showed no vasoconstrictor effect on the basal tone of rings with functional endothelium. However, when the rings were precontracted with phenylephrine, both drugs were able to induce concentration-dependent vasorelaxation (Emax = 31.7 ± 3.3%, n = 6 for LIDO and 69 ± 8%, n = 6 for ROPI) that were not altered after removal of the endothelium (Emax = 28.7 ± 1.3%, n = 7 for LIDO and Emax = 58.8 ± 5.9%, n = 6 for ROPI). In rings without functional endothelium and precontracted with depolarizing Tyrode solution (80 mM KCl), the LIDO-induced vasorelaxation was no significantly changed (Emax = 29 ± 3%, n = 7). However, ROPI-induced vasorelaxation was reduced in this protocol and the presence of 1 mM tetraethylammonium (TEA) (Emax = 21.2 ± 5.1%, n = 7 and Emax = 17.4 ± 3.7, n = 4, ...

Ethnopharmacological Properties of Ceasalpinia benthamiana - A Mini Review.

Caesalpinia benthamiana (Baill.) Herend. and Zarucchi (synonym. Mezoneuron benthamianum Baill.) belongs to the family Fabaceae, it is a climbing or a straggling shrub and is well known in some West African countries for its medicinal properties where it is used to cure general malaise, wound, urethral discharge, ulcer, pile, skin infection and believed to have aphrodisiac property. Phytochemical studies have revealed the leaf to contain essential oils, Gallic acid derivatives, tannins, saponins, flavonoids, phenols, anthraquinones and reducing sugars while the aqueous fractions of the root contain Gallic acid, resveratrol and tannins. Pharmacological assays have established the plant to be antiinflammatory, anti-diarrheal, anti-bacterial, anti-candida, and to have vasorelaxation and aphrodisiac properties. This review presents information on the morphology, ecology, ethnopharmacology, phytochemistry, biological activities and toxicological properties of C. benthamiana and aims at providing an up-to-date detail that should constitute baseline information for future research on the plant.

Korean Red Ginseng Water Extract Restores Impaired Endothelial Function by Inhibiting Arginase Activity in Aged Mice

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young (10+/-3 weeks) and aged (55+/-5 weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.

Antihypertensive and vasorelaxant effects of ethanol extract of stem barks from Zanthoxylum rhoifolium Lam in rats.

Administration of ethanol extract of stem bark from Z. rhoifolium (EEtOH-ZR) induced hypotension associated with a dual effect in heart rate in normotensive rats. This response was highlighted in spontaneously hypertensive rats (SHR). In rat superior mesenteric artery rings, the cumulative addition of EEtOH-ZR (0.1–750 µg/mL) on a phenylephrine-induced pre-contraction (10-5 M) promoted a vasorelaxant effect by a concentration-dependent manner and independent of vascular endothelium. A similar effect was obtained on KCl-induced pre-contractions (80 mM). EEtOH-ZR attenuated contractions induced by cumulative addition of CaCl2 (10-6–3 × 10-2 M) in depolarizing medium without Ca2+ only at 500 or 750 µg/mL. Likewise, on S-(–)-Bay K 8644-induced pre-contractions (10-7 M), the EEtOH-ZR-induced vasorelaxant effect was attenuated. EEtOH-ZR (27, 81, 243 or 500 µg/mL) inhibited contractions induced by cumulative addition of phenylephrine (10-9 - 10-5 M) in endothelium-denuded preparations or by a single concentration (10-5 M) in a Ca2+-free medium. The involvement of K+ channels was evaluated by tetraethylammonium (3 mM); the EEtOH-ZR-induced vasorelaxation was not attenuated. Thus, calcium influx blockade through voltage-operated calcium channels (CaVL) and inhibition of calcium release from intracellular stores are probably underlying EEtOH-ZR-induced cardiovascular effects.

Pharmacological potential of Populus nigra extract as antioxidant, anti-inflammatory, cardiovascular and hepatoprotective agent

Objective: To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract. Methods: Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema. Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections. Vasorelaxant effect was estimated in endothelium-intact and-rubbed rings of porcine coronary arteries precontracted with high concentration of U46619. Results:The results showed a moderate antioxidant activity (40%), but potent anti-inflammatory activity (49.9%) on carrageenan-induced mice paw edema, and also as revealed by histopathologic examination, complete protection against AlCl3-induced hepatic toxicity. Relaxant effects of the same extract on vascular preparation from porcine aorta precontracted with high concentration of U46619 were considerable at 10-1 g/L, and comparable (P>0.05) between endothelium-intact (67.74%, IC50=0.04 mg/mL) and-rubbed (72.72%, IC50=0.075 mg/mL) aortic rings. Conclusions: The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca2+influx.

Centaurium cachanlahuen (Mol) Robinson, a Chilean native plant with a vasodilatory effect / Centaurium cachanlahuen (Mol) Robinson una planta nativa chilena con efecto vasodilatador

Centaurium cachanlahuen (Mol.) Robinson is a chilean native plant widely used in traditional medicine for the treatment of many diseases, including cardiovascular disorders. Studies carried out in normal and hypertensive rats suggested that extract of Centaurium cachanlahuen has antihypertensive effect. In this work, we aim to evaluate the effect of aqueous and hydroalcoholic extracts of Centaurium cachanlahuen on the vascular reactivity using rat aorta rings precontrated with phenylephrine (0.1 uM). Results showed that both aqueous (3 mg/mL) and hydroalcoholic extracts (3 mg/mL) produced rat aorta vasodilatation that was higher (P < 0.001) in the hydroalcoholic extract compared to the aqueous extract. This effect had an important endothelium-dependent component that was mediated by nitric oxide (NO), as supported by the inhibition of the response in the presence of N-nitro-L-arginine (L-NNA, 100 uM), a nitric oxide synthase (NOS) inhibitor. We suggest that xanthones present in the plant may play a key role in the vasodilator effect of Centaurium cachanlahuen extracts. The present study provides experimental evidence supporting the folkloric use of Centaurium cachanlahuen as hypotensive agent.

Centaurium cachanlahuen (Mol) Robinson es una planta nativa chilena ampliamente utilizada en medicina tradicional para el tratamiento de varias enfermedades, que incluyen alteraciones cardiovasculares. Estudios llevados a cabo en ratas normales e hipertensas sugieren que el extracto de Centaurium cachanlahuen tiene efecto antihipertensivo. El propósito de este trabajo fue evaluar el efecto de extractos acuosos e hidroalcohólicos de Centaurium cachanlahuen sobre la reactividad vascular de aorta de rata precontraída con fenilefrina (0.1 uM). Tanto el extracto acuoso (3 mg/mL) como el extracto hidroalcohólico (3 mg/mL) produjeron relajación de aorta de rata, la cual fue de mayor magnitud (P < 0.001) con el extracto hidroalcohólico respecto del extracto acuoso. El efecto observado tuvo un importante componente mediado por óxido nítrico (NO), tal como lo demuestra la inhibición de esta respuesta en presencia de N-nitro-L-arginina (L-NNA, 100 uM), un inhibidor de la óxido nítrico sintasa (NOS). Se sugiere que las xantonas presente en la planta pueden jugar un papel clave en el efecto vasodilatador observado por los extractos de Centaurium cachanlahuen. Este estudio constituye una evidencia experimental que apoya el uso popular de Centaurium cachanlahuen como agente hipotensor.