Vasorelaxant effects of biochemical constituents of various medicinal plants and their benefits in diab

Endothelial function plays a pivotal role in cardiovascular health,and dysfunction in this context diminishes vasorelaxation concomitant with endothelial activity.The nitric oxide-cyclic guanosine monophosphate pathway,prostacyclin-cyclic adenosine monophosphate pathway,inhibition of phosphodiesterase,and the opening of potassium channels,coupled with the reduction of calcium levels in the cell,constitute critical mechanisms governing vasorelaxation.Cardiovascular disease stands as a significant contributor to morbidity and mortality among individuals with diabetes,with adults afflicted by diabetes exhibiting a heightened cardiovascular risk compared to their non-diabetic counterparts.A plethora of medicinal plants,characterized by potent pharmacological effects and minimal side effects,holds promise in addressing these concerns.In this review,we delineate various medicinal plants and their respective biochemical constituents,showcasing concurrent vasorelaxant and anti-diabetic activities.

Acute Oral Toxicity and Vasorelaxant Effects of Hydroethanolic Extract from Lannea microcarpa Engl. & K. Krause (Anacardiaceae) Trunk Barks in Mice Aortas: Possible Involvement of Intracellular Ca 2+ Mobilization

Lannea microcrapa Engl. & K. Krause (Anacardiaceae) is a fruit and medicinal plant widely used in Burkina Faso. This plant is traditionally used in the treatment of hypertension. The aim of the present study was to evaluate the vasorelaxant effects of the hydroethanolic extract from Lannea microcarpa trunk barks (HE_ELM) on the aorta isolated from NMRI mice. Phytochemical screening by HPTLC, assay of phenolic and flavonoid compounds, assessment of antioxidant activity (DPPH, ABTS, FRAP, and LPO), and myography of HE_ELM (1 - 2000 μg/mL) on mice thoracic aortas in the presence and absence of endothelium were carried out. Endothelium-dependent and endothelium-independant vasodilation were assessed by cumulative addition of Ach (1 nM - 10 μM) on aortic rings precontracted with the thromboxane analogue A2 agonist, 9,11-dideoxy9α,11α-methanoepoxy PGF2α (U46619). L-NAME was used to verify the involvement of NO production in the relaxation mechanism of the extract. Acute oral toxicity of HE_ELM was also evaluated. A phytochemical study revealed the presence of tannins, flavonoids, sterols and triterpenes, saponosides, and high levels of total phenolics and flavonoids. These compounds are thought to be responsible for the extract’s antioxidant and vasorelaxant properties. HE_ELM demonstrated significant antioxidant potential and induced aortic relaxation. Indeed, pharmacological parameters gave EC50 values ranging from 596.45 ± 95.82 μg/mL to 749.48 ± 133.40 μg/mL and Emax values from 85.51% ± 9.59% to 96.81% ± 8.60% for the three conditions of vasodilation of the extract (p > 0.05). A complete antagonism of the contractile effect of U46619 was noted with 1 mg/mL HE_ELM. These results suggest that HE_ELM induces aortic relaxation through a concentration-dependent, endothelium-independent mechanism, possibly involving intracellular calcium mobilization of vascular cells. Acute oral toxicity tests of HE_ELM (2000 mg/kg) showed no mortality or adverse effects, suggesting the extract’s safety and potential as a therapeutic agent for hypertension. This discovery scientifically validates the use of the plant in alternative medicine to treat hypertension.

Vasorelaxant activity of extracts obtained from Apium graveolens:Possible source for vasorelaxant molecules isolation with potential antihypertensive effect

Objective:To investigate the vasorelaxant effect of organic extracts from Apium graveolens(A.graveolens)which is a part of a group of plants subjected to pharmacological and phytochemical study with the purpose of offering it as an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.Methods:An ex vivo method was employed to assess the vasorelaxant activity.This consisted of using rat aortic rings with and without endothelium precontracted with norepinephrine.Results:All extracts caused concentration-dependent relaxation in precontracted aortic rings with and without endothelium;the most active extracts were Dichloromethane and Ethyl Acetate extracts from A.graveolens.These results suggested that secondary metabolites responsible for the vasorelaxant activity belong to a group of compounds of medium polarity.Also,our evidence showed that effect induced by dichloromethane and ethyl acetate extracts from A.graveolens is mediated probably by calcium antagonism.Conclusions:A.graveolens represents an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects.

The vasorelaxant effect of pinocembrin on the rat basilar artery and its potential mechanisms

Aim To evaluate the vasorelaxant effects of the flavonone pinocembrin in isolated rat basilar artery rings and to investigate its possible mechanisms. Methods The isotonic contractions of the basilar artery rings from SD rats were recorded. Results Pinocembrin exerted vasorelaxation in a close-dependent manner in KCL （60 mmol · L^-1 ） or 5-HT （ 1 μmol · L^- 1）-induced sustained contraction and partial loss of the vasorelaxation in endothelium- denuded rings. Pretreatment with pinocembrin （30 or 50 μmol · L^-1 ） attenuated contractile responses to KC1 （ 10 - 60 mmol · L^-1 ） and 5-HT （0. 001 - 10 μmol · L^-1 ）. The pinocembrin -induced vasorelaxation was significant- ly reduced by the nitric oxide synthase inhibitor Nco-nitro-L-arginine methyl ester （L-NAME, 100 μmol · L^-1） , the guanylate cyclase inhibitor ODQ （5 μmol · L^-1） and the cyclooxygenase inhibitor indomethacin （5 μmol · L^-l）. The voltage-dependent K＋ channel blocker 4-aminopyridine （100 μmol · L^-1）, the ATP-sensitive K ＋ channel blocker glibenclamide （10μmol · L^-1） and Ca2＋-activated K ＋ channel blocker tetraethylammonium （1 retool· L^-1） remarkably attenuated pinocembrin-induced relaxations. Pinocembrin also inhibited contraction in- duced by increasing external calcium in Ca2＋-free medium plus 60 mmol · L^-1 KC1. Conclusion These results demonstrate that pinocembrin has a vasorelaxant effect on isolated rat basilar artery rings and may exert its action through an endothelium-dependent pathway, involving NO-cGMP, and also through an endothelium-independent 2＋ pathway, opening K ＋ channels and blockade of Ca channels.

Vasorelaxant effect of 7-[2-(4-morpholinyl)ethoxy]chroman hydrochloride(HEF-04) and possible mechanisms

This study aimed to investigate the relaxant effect of chroman compound HEF-04 on isolated vascular smooth muscle （VSM） and the possible underlying mechanisms involved. Isolated rabbit thoracic aorta was used as the in vitro model and the relaxant effects of HEF-04 on endothelium-intact （＋EC） and endothelium-denuded （EC） thoracic aortic rings were compared. Potassium channel blockers, guanylate cyclase inhibitors, and COX-inhibitors were used to explore associations between the relaxant effects of HEF-04 with potassium channels, NO, and prostaglandin-like substances and endothelial hyperpolafizing factor （EDHF）, respectively. The results indicated that HEF-04 （1 × 10^-5 mol/L to 3× 10^-3 mol/L） had no significant impact on basal vascular tension, but could relax the contraction of vascular smooth muscle caused by high-K＋ solution in a dose-dependent manner. Indomethacin （5.6× 10^-6 mol/L） had no effect on vasorelaxation effect of HEF-04. In contrast, the vasorelaxant effect of HEF-04 was enhanced by methylene blue, which was significantly inhibited by calcium-dependent potassium channel blocker TEA. The vasorelaxant effect of HEF-04 on ＋EC thoracic aortic rings was significantly stronger than that on -EC thoracic aortic rings. The endothelium dependent relaxant effect of HEF-04 on VSM might be attributed to the interaction of HEF-04 with vascular relaxing factors or the increased release of EDHF.

VASORELAXANT DITERPENES: FROM TRADITIONNAL MEDICINE TO NEW INHIBITORS OF VOLTAGE-DEPENDANT CALCIUM CHANNELS

Croton zambezicus Muell.Arg.(Euphorbiaceae)(Syn.C.amabilis Muell.Arg.,C.gratissimus Burch.)is a shrub or small tree reaching 10 m in height.The leaf decoction is used in Benin as anti-hypertensive,anti-microbial(urinary infections)and to treat fever associated with malaria.We analysed the in vitro and in vivo vasorelaxant activity

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 PEbut not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE-and KPSSinduced 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 smoothmuscle 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.

Vasorelaxant effect of osthole on isolated thoracic aortic rings in rats

OBJECTIVE: To investigate the effect of osthole on isolated thoracic aortic rings, and to determine the potential mechanism of action.METHODS: Thoracic aortas were isolated from Wistar rats, and were suspended in tissue organ chambers for vascular tension measurement. The effect of cumulative osthole(10-9, 10-8, 10-7, 10-6, and 10-5 mol/L) on endothelium-intact and endothelium-denuded thoracic aortic rings pre-contracted with phenylephrine(PE, 10-6 mol/L) or KCl(6 × 10-2 mol/L) was recorded. Histomorphological changes of thoracic aorta were analyzed by hematoxylin-eosin. The effects of different osthole concentrations on endothelium-intact aortic rings, which were pre-inhibited with the non-selective nitric oxide synthase inhibitor L-Arg(NO2)-OMe·HCl(3 × 10-4 mol/L), endothelium-derived nitric oxide synthase inhibitor Nω-nitro-L-arginine(3 × 10-4 mol/L), guanylate cyclase inhibitor 1 H-[1,2,4] oxadiazolo [4,3-α]quinoxaline-1-one(10-5 mol/L), cyclooxygenase inhibitor indometacin(10-5 mol/L), and the Ca2+-activated potassium channel inhibitor tetraethylammonium nitrate(10-5 mol/L), and then contracted with PE, were examined. Aortic rings incubated with osthole(10-5 mol/L), phentolamine(10-5 mol/L), or verapamil(10-5 mol/L) in Ca2+-free Krebs-Henseleit solution(KHS) were stimulated with PE or KCl.RESULTS: There was a dose-dependent increase in vasorelaxation of isolated thoracic aortic rings(both with and without endothelium) with increasing osthole concentration. Hematoxylin-eosin staining showed that osthole significantly improved thoracic aorta ring morphology. Compared with the control group, there were also significant differences after incubation with L-Arg(NO2)-OMe ω-nitro-L-arginine, and 1 H-[1,2,4] oxadiazo·lo HCl,N [4,3-α] quinoxaline-1-one(P < 0.05 for all). The relaxation rate of the rings in the osthole group incubated with indometacin and tetraethylammonium nitrate were similar to controls. In Ca2+-free KHS, the PE-induced contraction was similar between the osthole(4.37% ± 0.41%) and control(4.21% ± 1.33%)groups. However, after cumulative CaCl2(0.5, 1, 1.5,2, 2.5, and 3 mmol/L), the Ca2+-induced contraction was significantly inhibited in the osthole and phentolamine groups compared with controls(P < 0.05).After cumulative CaCl2 was added to Ca2+-free KHS(high K+ concentration), the contraction rate was significantly higher than both of the control and the osthole groups(P < 0.05). The contraction rate in the osthole group was higher than the verapamil group(P < 0.05).CONCLUSION: Osthole has a vasorelaxant effect on isolated rat thoracic aortic rings, via inhibition of both receptor-operated and voltage-dependent Ca2+channels in arterial smooth muscle, leading to decreased Ca2+ influx, and via inhibition of nitric oxide release on arterial endothelial cells.

Antihypertensive efficacy of extract of Hedera helix in high salt-induced hypertensive Sprague-Dawley rats

Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methanolic extract was prepared and the activity directed fractionation was carried out. Spectrophotometric analysis of total phenolic and flavonoid content was also done. HPLC analysis was performed for the detection of hederacoside C. In-vivo blood pressure study was carried out in normotensive and high salt-induced hypertensive SpragueDawley rats. Isolated aortic tissues from rat and rabbit were used for in-vitro studies. The effects were recorded and analyzed through PowerL ab data acquisition system. Results: Crude extract of H. helix(1-30 mg/kg) decreased blood pressure to greater extent in high salt-induced hypertensive rats in-vivo compared to the normotensive [Max. fall(58.59±0.02) mm Hg vs.(67.53±3.07) mmH g]. The n-hexane, chloroform, ethyl acetate and aqueous fractions were also checked. These fractions were more effective in hypertensive rats. Aqueous fraction was more potent and n-hexane the least. In isolated rat aortic rings precontracted with phenylephrine, crude extract induced endothelium-dependent effect. The endothelium-dependent component of vasodilatory effect was ablated with L-NAME, and denudation of endothelium. The aqueous fraction was most potent vasodilator. In aortic rings from hypertensive rats, extract and fractions produced partial endothelium-independent effect which was not affected by pretreatment with L-NAME, indicating endothelium dysfunction in the hypertensive rats and suggesting additional vasodilatory mechanisms. In rabbit aorta, the extract and fractions also inhibited phenylephrine and high K^+-induced precontractions, and shifted Ca^(++) concentration–response curves. Conclusions: Our findings indicate that extract and fractions of H. helix are antihypertensive remedies, which is the outcome of vasodilatory effect. This vasodilatory effect is mediated through nitric oxide and Ca^(++) antagonism.

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 Pupulus 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-nibbed rings of porcine coronary arteries precontracted with high concentration of U466I9.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 AlCl_3-induced hepatic toxicity.Relaxant effects of the same exlracl on vascular preparation from porcine aorta precontracted with high concentration of U466I9 were considerable at 10^(-1)g/L,and comparable(P>0.05)between endothelium-intact(67.74%,IC_(50)0.04 mg/ml.)and-rubbed(72.72%,IC_(50)=0.075 mg/ml,)aortic rings.Conclusions:The extract exerted significant anti-inflammatory,hepatoprotective and vasorelaxant activities,the latter being cndothelium-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 Ca^(2+)influx.

Vasodilator response to <i>Psidium guajave</i>leaves of mesenteric bed vessels from diabetic and non-diabetic rats

Mortality from cardiovascular abnormalities is almost three times more prevalent in the diabetic population than that in the general population. Psidium guajave has been used traditionally for a long time as a medicinal herb to cure diabetes. Endothelial dependent vasorelaxation effect of Psidium guajave extract on normal aortic rings was observed. This study was designed to investigate the endothelium and nitric oxide roles inPGE-induced vasorelaxation in diabetic rat vessel. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Eight weeks later, superior mesenteric arteries of non-diabetic and diabetic groups were isolated and perfused according to the McGregor method. Prepared vascular beds were constricted with phenylephrine to induce 70% - 75% of maximal constriction. Psidium guajave extract at concentrations of 0.1 to 4 mg/100ml added to the medium and perfusion pressure was recorded. Baseline perfusion pressure of diabetic group was significantly higher than non-diabetic rats in both intact and denuded endothelium. Psidium guajave extract caused a significantly dose depended decrease in perfusion pressure in non-diabetic and diabetic groups in both intact and denuded endothelium. In the presence of N (ω)-nitro-L-arginine methyl ester, Psidium guajave ex-tractinduced relaxation in intact mesenteric beds of non-diabetic and diabetic animals was not suppressed. From the results of this study, it may be concluded that vasorelaxatory effect of Psidium guajave extract is not mediated by endothelium and nitric oxide in both diabetic and non-diabetic vessel and supports the use of the plant’s leaves as a natural, adjunct phytomedicine in the management of diabetes vessel complications.

Four new corynanthe-type alkaloids from the roots of Alstonia scholaris

Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.

Vasorelaxation Effect of Gastrodin on Isolated Thoracic Aorta Rings of Rats

Objective： To study the effect of gastrodin on isolated thoracic aorta rings of rats and to investigate the potential mechanism. Methods： A perfusion model of isolated thoracic aorta rings of rats was applied. The effect of cumulative gastrodin （5, 50, 100,150, 200, and 250 μ mol/L） on endothelium-intact aorta rings was investigated. The same procedure was applied to observe the effect of gastrodin on endotheliumintact/denuded aorta rings pre-contracted with 10.8 mol/L phenylephrine hydrochloride （PE）. The aorta rings incubated by 200 mmol/L gastrodin in the Ca2＋-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 KCI was also observed. Results： Compared with the denuded gastrodin group, the intact gastrodin group could significantly relax the PE-contracted aorta rings （P〈0.01）. In Ca2＋-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 Ca2＋-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 KCI-contracted gastrodin group （96.3%± 0.6%） was not significantly different from that in the control group （96.8± 1.2%）. Conclusions： 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 Ca2. released from the sarcoplasmic reticulum.

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^(2+)]_i, 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 KATPchannel activation in smooth muscle cells of arteries.Triclosan treatment increased cytosolic [Ca^(2+)]_i, 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 in vivo.

Hydrogen sulfide and vascular relaxation

Objective To review the vasorelaxant effects of hydrogen sulfide （H2S） in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved. Data sources The data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms ＂hydrogen sulfide＂ and ＂vascular relaxation＂. Study selection Articles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected. Results H2S plays an important role in the regulation of cardiovascular tone. The vasomodulatory effects of H2S depend on factors including concentration, species and tissue type. The H2S donor, sodium hydrosulfide （NariS）, causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner. This effect was more pronounced than that observed in pulmonary arterial rings. The expression of KATp channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings. H2S is involved in the pathogenesis of a variety of cardiovascular diseases. Downregulation of the endogenous H2S pathway is an important factor in the pathogenesis of cardiovascular diseases. The vasorelaxant effects of H2S have been shown to be mediated by activation of KATP channels in vascular smooth muscle cells and via the induction of acidification due to activation of the Cr/HCO3 exchanger. It is speculated that the mechanisms underlying the vasoconstrictive function of H2S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation. Conclusion H2S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure.

Mechanisms underlying the vascular relaxation activities of Zingiber officinale var. rubrum in thoracic aorta of spontaneously hypertensive rats

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 Nω-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 Ca2+-dependent contraction and influenced the ratio of the responses to phenylephrine in Ca2+-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-KATP channels, stimulation of muscarinic receptors, and transmembrane calcium channel or Ca2+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

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^(-3), 10^(-2), 10^(-1) 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 Nx-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^(2+)-activated potassium channels.

Vascular insulin resistance in prehypertensive rats contributes to the development of hypertension:Role of PI3 kinase/Akt/eNOS signaling

Objective: It is well known that systemic insulin resistance (IR) is closely associated with the metabolic syndrome including type 2 diabetes and hypertension. However, it remains