Rat Aortic Preparations Research Articles

Effect of hydrogen sulfide on the contractile activity of smooth muscle cells from the rat aorta

In preparations of rat aorta, used as a model of muscular type arteries, the method mehanografii studied the effect of hydrogen sulfide on the reduction of isolated of vascular smooth muscle. Found that hydrogen sulfide in concentrations 1—50 mmol increases the mechanical stress of smooth muscle in high-K + medium. At higher concentrations (300—1 000 mmol) H2S leads to lower amplitude giperkalievoy contraction in high-K + medium. Reduction of smooth muscle cells caused by phenylephrine inhibited the action of hydrogen sulfide in the whole range of concentrations. The causes of differences in data obtained with the results of studies in other laboratories, and possible mechanisms of action of hydrogen sulfide on the contractile activity of vascular smooth muscle.

EFFECTS of Zoledronic ACID On eNOS Exppression and Vascular Contractility IN Rat Aorta

AbstractAbstract 4318Zoledronic acid (ZOL) is a potent nitrogen-containing bisphosphonate used in the treatment of skeletal metabolic disorders and bone metastatic diseases. It has been shown that the nitrogenous bisphosphonates inhibits enzymes of mevalonate pathway. Similar with statin derivatives, ZOL affects the biological activity of geranyl-geranylated proteins in mevalonate pathway, as shown for the small GTPase RhoA. Although, beneficial effects of statin derivatives on vascular tissue have been reported, there is no study on effects and of ZOL on endothelial functions in vascular tissue and mechanisms of its action. It is important to elucidate the mechanism regulating NO production for endothelial cells to develop new therapeutic strategies for the treatment of impaired endothelial function associated with the vascular diseases. The aim of this study is to demonstrate the molecular mechanism of ZOL in the regulation of endothelial responses and eNOS expression in rat aorta. For his aim, potassium chloride and phenyleprine induced vasoconstriction was evaluated in endothelium intact and denuded isolated rat aorta preparations (n=6) after incubation with ZOL 100 μM and the results were compared with those without ZOL incubation. In addition, to evaluate endothelium dependent or independent effects of ZOL, vasodilator effects of acetylcholine and sodium nitroprussid were tested in the presence and absence of ZOL. To evaluate the influence of protein geranylation in effect of ZOL, contractile effect of phenylephrine vasocontractions was tested after incubation with ZOL in the presence of geranylgeranyl pyrophosphate and farnesyl pyrophosphate, important enzymes of mevolonate pathway. In addition, eNOS mRNA expressions were evaluated with RT-PCR in intact rat aorta or after incubation with ZOL. According to our results, incubation with ZOL decreased potassium chloride and phenylephrine-induced contractions significantly. This decrease was reversed NO-syntase inhibitor Nı,-nitro-L-arginine methyl esther (L-NAME) 0.1mM. Additionally, incubation with ZOL, increased endothelium-dependent acethycholine-induced relaxations and this effect of ZOL was inhibited by L-NAME. In rat aorta preparations incubated with ZOL, eNOS mRNA expression was increased significantly (1.52 fold) compared with control group. According to these results, we herein provide the first experimental evidence for the physiological role of ZOL in the regulation of eNOS expression and the contractility in the vascular tissues. This effect of ZOL is probably via its influence on RhoA. Since the restoration of NO bioactivity is a major target of present pharmacological and non-pharmacological treatments in cardiovascular medicine, further laboratory and clinical studies to explore the effect of ZOL on vascular endothelium may be helpful to demonstrate the possible benefits. Disclosures:No relevant conflicts of interest to declare.

Endothelium-dependent and -independent relaxations in aortic rings obtained from hypertensive hooded (Aguti) rats.

Experimental hypertension studies are few in the hooded (Aguti) rat. The present study was designed to investigate the usefulness of this rat strain for experimental hypertension studies and to test the hypothesis that the hypertension may be associated with a diminution of endothelium dependent and independent relaxations. Hypertension was induced in inbred hooded rats (n=8 each) by administering 8% salt in the diet and /or 100 mg/kg/day Nomega-nitro-L-arginine-methyl-ester (L-NAME) in the drinking water for six and/or four weeks respectively. The rats were anaesthetized using a 25% urethane and 1% chloralose mixture given intraperitoneally at a dose of 5 mg/kg. Their blood pressure was measured invasively. Thereafter, relaxations of rat aortic preparations to acetylcholine, histamine and sodium nitroprusside (SNP) were assessed using standard organ bath conditions. Probability level of 0.05 was taken as statistically significant. The mean arterial pressure (MAP;mm Hg) rose significantly in all test groups (Salt: 148.3 +/- 4.6; L-NAME: 181.7 +/-8.3; Salt+L-NAME:154.9 +/-8.7) compared with control (94.2 +/-6.8; [P < 0.05]. The MAP was significantly [P < 0.05] higher in the L-NAME group than in all the other groups. The heart rate fell significantly in the salt + L-NAME group compared to control [P <0.05].The IC50 of acetylcholine in aortic rings from L-NAME rats (7.9 x 10(-1) +/- 6.0 x 10(-3)) was significantly higher than in rings from control (9.4 x 10(-8) +/- 2.8 x 10(-8)), salt (7.8 x 10(-7) +/- 4.7 x 10(-7)) and salt + L-NAME (3.3 x 10 (-7) +/- 2.1 x 10(-7)) rats [P < 0.05]. The IC50 of histamine and SNP in the rings from the test groups of rats showed no significant difference from control. Also, endothelium dependent and independent relaxations were preserved in the various forms of hypertension studied except in chronic NOS inhibition where the former was attenuated in response to acetylcholine.

In vitro vascular effects of chloroquine in rat aortic strip preparation

In vitro vascular effects of chloroquine in rat aortic strip preparation

Blood Pressure-lowering and Vascular Modulator Effects of Acorus calamus Extract Are Mediated Through Multiple Pathways

This investigation was aimed to provide a pharmacologic basis to the medicinal use of Acorus calamus in cardiovascular disorders. In normotensive anesthetized rats, crude extract of Acorus calamus and its ethylacetate and nHexane fractions caused a fall in mean arterial pressure. In rabbit aorta rings, crude extract was more potent against high K (80 mM), ethylacetate against phenylephrine (1 microM), whereas nHexane fraction was equipotent against both precontractions. Crude extract exhibited a vasoconstrictor effect on baseline. Pretreatment of aortic rings with crude extract and its fractions shifted Ca concentration-response curves to the right, similar to verapamil. Crude extract and ethylacetate fraction suppressed phenylephrine peak formation in Ca-free medium. In rat aorta preparations, crude extract exhibited endothelium-independent relaxation with a vasodilatory effect against high K. nHexane fraction caused an endothelium-dependent Nomega-nitro-l-arginine methyl ester-sensitive vasorelaxant along with ryanodine-sensitive vasoconstrictor effect on baseline tension and partially inhibited high K, although ethylacetate fraction caused an endothelium-independent relaxant and endothelium-dependent vasoconstrictor effect. These data indicate that crude extract possesses a combination of effects, relaxant effects mediated possibly through Ca antagonism in addition to a nitric oxide pathway, although the associated vasoconstrictor effects may be meant by nature to offset excessive vasodilatation, thus providing a pharmacologic rationale to its cardiovascular medi-cinal uses.

Endothelium-dependent vasorelaxation in rat thoracic aorta by Mansoa hirsuta D.C.

The vasodilator effect of the ethanolic extract of Mansoa hirsuta leaves (EEF) was assayed in rat aortic rings. EEF produced a concentration-dependent vasodilatation (pIC(50)=5.1+/-0.2), which was absent in endothelium-denuded vessels. The vasodilator effect of EEF was similar to a standardized ethanolic extract of Hancornia speciosa Gomes (pIC(50)=5.1+/-0.1). The endothelium-dependent vasodilatation induced by EEF was abolished by L-NAME (100 microM), a nitric oxide (NO) synthase inhibitor, but not by indomethacin (10 microM; pIC(50)=4.9+/-0.2), a cyclooxygenase inhibitor. The concentration-response curve of EEF was not modified by the addition of superoxide dismutase (SOD; 300 U/ml). In addition, EEF (50 microg/ml) displaced the 3-morpholino-sidnonimine (SIN-1; p<0.05) concentration-effect curve to the left, as well as SOD (300 U/ml). These findings lead us to conclude that EEF induces a NO- and endothelium-dependent vasodilatation in rat aortic preparations, and that this effect is, at least in some extent, due to an increase in the NO bioavailability as consequence of its antioxidant activity. The HPLC-DAD profile recorded for EEF indicates the presence of four major peaks with close retention times, exhibiting similar UV spectra with wavelength maxima compatible with heterogeneous proanthocyanidins.

Antihypertensive, vasorelaxant and inotropic effects of an ethanolic extract of the roots of Saururus chinensis

Aim of the study The present study was performed to evaluate the cardiovascular effects of ethanolic extract of the roots of Saururus chinensis (EERSC) in rats. Materials and Methods The effects of EERSC on the vascular responses of isolated rat aorta, the cardiac functions in isolated rat heart, and the antihypertensive effects in spontaneously hypertensive rats (SHRs) were evaluated. Results In isolated rat aortic preparations, EERSC exhibited a potent vasorelaxant effect with EC 50 value of 9.1 μg/ml. This relaxation was significantly inhibited by denudation of endothelial layer or by pretreatment with N G-nitro- l-arginine methyl ester. In addition, the raising extracellular K + (45 mM), or pretreatment with tetraethylammonium (10 mM) significantly inhibited EERSC-induced vasorelaxation in endothelium-denuded aortic rings. In isolated rat hearts, EERSC significantly reduced cardiac functions such as left ventricle pressure and heart rate. In an antihypertensive study with SHRs, long-term oral administrations of EERSC decreased blood pressure of SHRs (approximately 20 mmHg). Conclusions These results suggest that chronic treatment with EERSC exerts an antihypertensive effect in SHRs, and its direct vasorelaxant properties and negative inotropic actions may contribute to reduce the elevated blood pressure.

Serotonergic Properties of the Roots of Clerodendron capitatum

The aim of this study is to investigate the pharmacological effects of the methanolic extract of Clerodendron capitatum, CC, (family verbenaceae). These investigations were carried out on isolated frog rectus abdominus muscle and rabbit aortic strips and jejunum and non-pregnant rat uterus pretreated with oestradiol. Results showed that CC did not demonstrate any contracting, relaxant or blocking effects on frog rectus abdominus muscle and rat aortic strip preparations. The extract produced a concentration-dependent (p<0.05, t-test, n = 6) decrease of the normal rhythmic contraction of rabbit jejunum, however, this effect was reversed by prior addition of cyproheptadine (non-specific 5-HT antagonist). In addition, CC also produced a stimulant activity on rat uterus which was blocked by cyproheptadine. Future study is recommended to study the specificity of CC to different 5-HT receptors by using different isolated animal tissues and specific 5-HT antagonists.

Attenuation of maitotoxin-induced cytotoxicity in rat aortic smooth muscle cells by inhibitors of Na +/Ca 2+ exchange, and calpain activation

The highly potent marine toxin maitotoxin (MTX) evoked an increase in cytosolic Ca 2+ levels in fura-2 loaded rat aortic smooth muscle cells, which was dependent on extracellular Ca 2+. This increase was almost fully inhibited by KB-R7943, a potent selective inhibitor of the reverse mode of the Na +/Ca 2+ exchanger (NCX). Cell viability was assessed using ethidium bromide uptake and the alamarBlue cytotoxicity assay. In both assays MTX-induced toxicity was attenuated by KB-R7943, as well as by MDL 28170, a membrane permeable calpain inhibitor. Maitotoxin-evoked contractions of rat aortic strip preparations in vitro, which persist following washout of the toxin, were relaxed by subsequent addition of KB-R7943 or MDL 28170, either in the presence of, or following washout of MTX. These results suggest that MTX targets the Na +/Ca 2+ exchanger and causes it to operate in reverse mode (Na + efflux/Ca 2+ influx), thus leading to calpain activation, NCX cleavage, secondary Ca 2+ overload and cell death.

Cardiovascular Effects of Lignans Isolated from Saururus chinensis

Saururus chinensis has been widely used as a traditional medicine for the treatment of beriberi, hypertension, pneumonia, edema, jaundice and gonorrhea. However, there is only limited information on the cardiovascular effects of S. chinensis extract or its single compounds. The present study was performed to investigate the effects of active lignans isolated from the extract of S. chinensis on vascular responses and heart functions. The vasorelaxant activity-guided fractionation of roots extract of S. chinensis led to the isolation of eight lignans as active principles. These lignans produced concentration-dependent relaxations of the endothelium-intact aortic preparations of rat aorta. Particularly, saucerneol ( 1), saucerneol D ( 2) and machilin D ( 8) exhibited distinctive vasorelaxant activity (EC (50) values: 2.2, 12.7 and 17.8 microM, respectively), which were significantly inhibited by removal of functional endothelium or pretreatment with N(G)-nitro-L-arginine methyl ester. Saucerneol ( 1) and saucerneol D ( 2) caused a significant decrease in left ventricular pressure, +dP/dt (max) and heart rate in isolated hearts. These results suggest that several lignans including saucerneol ( 1), saucerneol D ( 2) and machilin D ( 8), isolated from the ethanol extract of the roots of S. chinensis, have significant cardiovascular effects such as vasorelaxant and negative inotropic actions.

Vasorelaxing Alkaloids and Flavonoids from Cassytha filiformis

Two new aporphine alkaloids, isofiliformine ( 1) and cassythic acid ( 3), along with 22 known compounds were isolated from whole herb of Cassytha filiformis. Cassythic acid ( 3), cassythine ( 4), neolitsine ( 7), and dicentrine ( 8) had potent vasorelaxing effects on precontracted rat aortic preparations with mean IC 50 values between 0.08 and 2.48 microM. Compounds 1, 1,2-methylenedioxy-3,10,11-trimethoxyaporphine ( 2), (-)- O-methylflavinatine ( 10), (-)-salutaridine ( 11), isohamnetin-3- O-beta-glucoside, and isohamnetin-3- O-rutinoside exerted moderate vessel-relaxing activities with IC 50 values from 16.50 to 32.81 microM at the test concentrations.

Inhibition of inducible nitric oxide production and iNOS protein expression in lipopolysaccharide-stimulated rat aorta and Raw 264.7 macrophages by ethanol extract of a Chinese herbal medicine formula (RCM-101) for allergic rhinitis

Aim of the study A Chinese herbal formula (RCM-101) has shown to be effective in reducing symptoms of seasonal allergic rhinitis (SAR) in a randomised, placebo-controlled clinical trial. The aim of this study is to investigate the effects of RCM-101 on the actions and synthesis of nitric oxide (NO). l-Arginine-induced endothelium-independent relaxations were studied in rat isolated aorta which was pre-treated with lipopolysaccharide (LPS). Materials and methods NO production and inducible nitric oxide synthase (iNOS) protein expression were studied in LPS and interferon γ-stimulated murine macrophages (Raw 264.7), measured by NO sensors and Western blotting. Results In rat aortic preparations, RCM-101 significantly inhibited endothelium-independent relaxations to l-arginine, but not affected those to sodium nitroprusside (SNP). In Raw 264.7 cells, RCM-101 and some of its individual ingredients (e.g., Radix glycyrrhizae, Radix bupleuri, Radix saposhnikoviae and Atractylodis rhizome macrocephalae) significantly inhibited the NO production and iNOS protein expression. Conclusions The findings indicate that RCM-101 may inhibit inducible NO production by suppressing iNOS. In addition, its inhibitory action of iNOS is likely to be mediated by several key herbal ingredients.

Cardiovascular inhibitory effects of Hyoscyamus niger

This study describes the hypotensive, cardiosuppressant and vasodilator activities of Hyoscyamus niger crude extract (Hn.Cr). Hn.Cr, which tested positive for alkaloids, coumarins, flavonoids, sterols, tannins and terpenes, caused a dose-dependent (10-100 mg/kg) fall in the arterial blood pressure (BP) of rats under anesthesia. In guinea-pig atria, Hn.Cr exhibited a cardiodepressant effect on the rate and force of spontaneous atrial contractions. In isolated rabbit aorta, Hn.Cr (0.01-1.0 mg/ml) relaxed the phenylephrine (PE, 1 microM) and K(+) (80 mM)-induced contractions and suppressed PE (1 microM) control peaks obtained in Ca(++)-free medium similar to that caused by verapamil. The vasodilator effect of Hn.Cr was endothelium-independent as it was not opposed by N (omega)-nitro-L-arginine methyl ester in endothelium-intact rat aortic preparations and also occurred at a similar concentration in endothelium-denuded tissues. These data indicate that Hyoscyamus niger lowers BP through a Ca(++)-antagonist mechanism.

Antihypertensive, Vasorelaxant, and Antioxidant Effect of Root Bark of Ulmus macrocarpa

The present study was performed to evaluate the cardiovascular effects of ethanolic extract from the root bark of Ulmus macrocarpa (RBUM) in rats. The effects of RBUM on the vascular response of isolated rat aorta and the blood pressure of spontaneously hypertensive rats (SHRs) were evaluated. In addition, its antioxidant activity in H9c2 cells was investigated. In the free radical scavenging assay using 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH), RBUM exhibited significant scavenging activity with an EC50 value of 14.3 microg/ml. RBUM also induced resistance to hydrogen peroxide-mediated oxidative insult in H9c2 myocardial cells. In isolated rat aortic preparations, RBUM exhibited potent vascular relaxant effect with an EC50 value of 1.9 microg/ml. This relaxation was significantly inhibited by denudation of the endothelial layer, pretreatment with NG-nitro-L-arginine methyl ester (10 microM), raising extracellular K+ (45 mM), and pretreatment with tetraethylammonium (10 mM). In an antihypertensive study with SHRs, long-term administration with RBUM (100 mg/kg) for 42 d decreased systolic blood pressure (approximately 20 mmHg). In SHRs after 42 d of treatment, RBUM recovered aortic relaxation to acetylcholine and sodium nitroprusside, and attenuated lipid peroxidation in liver of SHRs. These results suggest that chronic treatment with RBUM exerts antihypertensive effects in SHRs, and its direct vasorelaxant and antioxidant properties may contribute to reduce elevated blood pressure.

Theoretical and electrophysiological evidence for axial loading about aortic baroreceptor nerve terminals in rats

Arterial baroreceptors are essential for neurocirculatory control, providing rapid hemodynamic feedback to the central nervous system. The pressure-dependent discharge of carotid and aortic baroreceptor afferents has been extensively studied. A common assumption has been that circumferential deformation of the arterial wall is the predominant mechanical force affecting baroreceptor discharge. However, in vivo the arterial tree is under significant longitudinal tension, leading to the hypothesis that axially directed forces may contribute to baroreceptor function. To test this hypothesis, we utilized a combination of finite element modeling methods and an in vitro rat aortic arch preparation. Model formulation utilized traditional analytic constructs available in the literature followed by refinement of model material parameters through direct comparison of computationally and experimentally generated pressure-diameter curves. The numerical simulations strongly indicated a functional role for axial loading within the region of the baroreceptive nerve terminal. This prediction was confirmed through single-fiber recording of baroreceptor nerve discharge under conditions with and without longitudinal tension in the vessel preparation. The recordings (n = 5) demonstrated that longitudinal tension significantly (P < 0.02) lowered both the pressure threshold (P(th), mmHg) for baroreceptor discharge and sensitivity (S(th), Hz/mmHg). The effect was nearly instantaneous and sustained; i.e., under longitudinal tension average P(th) was 84 +/- 3 mmHg and S(th) was 0.71 +/- 0.15 Hz/mmHg, which immediately increased to a P(th) of 94 +/- 4 mmHg and a S(th) of 1.20 +/- 0.32 Hz/mmHg with loss of axial tension. Possible explanations of how an abrupt change in axial loading could result in a synchronized increase in afferent drive of the baroreceptor reflex, and the potentiating effect this could have on neurogenically mediated orthostatic intolerance are discussed.

The Effects of Chronic Treatment with Morus bombycis KOIDZUMI in Spontaneously Hypertensive Rats

The present study was performed to evaluate the antihypertensive effects of Morus bombycis KOIDZUMI (MK) in spontaneously hypertensive rats (SHRs). In addition, the effects on vascular responses and cardiac functions were also investigated. In isolated rat aortic preparations, the 100% ethanol extract of MK exhibited a potent vascular relaxant effect with IC(50) value of 3.9 microg/ml, and this vasorelaxant effect was completely abolished by pretreatment of the aortic tissues with N(G)-nitro-L-arginine methyl ester or the denudation of endothelial layer. In isolated rat hearts, the MK extract significantly reduced cardiac functions such as left ventricular developed pressure and heart rate. In an antihypertensive study in SHRs, long-term administration with MK extracts (10, 30, 100 mg/kg) for 42 d dose-dependently decreased systolic blood pressure (approximately 20 mmHg). In SHRs, MK extract enhanced the aortic relaxation to acetylcholine and sodium nitroprusside after 42 d of treatment. In addition, lipid peroxidation and DNA damage in liver of SHRs were also attenuated by long-term treatment with MK extract. These results suggest that chronic treatment with MK extract exerts an antihypertensive effect in SHRs, and its direct vasorelaxant, negative inotropic actions, and anti-oxidant properties may contribute to reduce the elevated blood pressure.

Distinct Activity of Peptide Mimetic Intracellular Ligands (Pepducins) for Proteinase‐Activated Receptor‐1 in Multiple Cells/Tissues

Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, can be activated not only by PAR1-activating peptides (PAR1APs) based on the N-terminal cryptic tethered ligand sequence but also by an N-palmitoylated (Pal) peptide, Pal-RCLSSSAVANRSKKSRALF-amide (P1pal-19), based on the intracellular loop 3 of PAR1, designated pepducin, in human platelets or PAR1-transfected cells. The present article evaluated the actions of P1pal-19 and also the shorter peptide, Pal-RCLSSSAVANRS-amide (P1pal-12), known as a possible PAR1 antagonist, in multiple cells/tissues that naturally express PAR1. P1pal-19 as well as a PAR1AP, TFLLR-amide, evoked cytosolic Ca(2+) mobilization in cultured human lung epithelial cells (A549) and rat gastric mucosal epithelial cells (RGM1). P1pal-19 and TFLLR-amide, but not a PAR2-activating peptide, SLIGRL-amide, caused delayed prostaglandin E(2) formation in RGM1 cells. P1pal-19, like TFLLR-amide, produced endothelial NO-dependent relaxation in rat aorta and epithelial prostanoid-dependent relaxation in mouse bronchus. The P1pal-19-induced relaxation remained constant even after desensitization of PAR1 with TFLLR-amide in either tissue. P1pal-19 failed to mimic the contractile effects of TFLLR-amide in the endothelium-denuded preparations of rat aorta or superior mesenteric artery and the rat gastric longitudinal smooth muscle strips. P1pal-12 partially inhibited the vasorelaxation caused by TFLLR-amide and P1pal-19, but not SLIGRL-amide, in the rat aorta. Our data thus indicate that P1pal-19 is capable of mimicking the effects of PAR1APs in the endothelial and epithelial, but not smooth muscle, cells/tissues, and suggest that P1pal-12 may act as a PAR1 antagonist in the vascular endothelium.

Inhibition of Release of Vasoactive and Inflammatory Mediators in Airway and Vascular Tissues and Macrophages by a Chinese Herbal Medicine Formula for Allergic Rhinitis

Herbal therapies are being used increasingly for the treatment of allergic rhinitis. The aim of this study was to investigate the possible pharmacological actions and cellular targets of a Chinese herbal formula (RCM-101), which was previously shown to be effective in reducing seasonal allergic rhinitis symptoms in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated tissues (trachea and aorta) were used to study the effects of RCM-101 on responses to various mediators. Production of leukotriene B4 in porcine neutrophils and of prostaglandin E2 and nitric oxide (NO) in Raw 264.7 cells were also measured. In rat and guinea pig tracheal preparations, RCM-101 inhibited contractile responses to compound 48/80 but not those to histamine (guinea pig preparations) or serotonin (rat preparations). Contractile responses of guinea pig tracheal preparations to carbachol and leukotriene C4, and relaxant responses to substance P and prostaglandin E2 were not affected by RCM-101. In rat aortic preparations, precontracted with phenylephrine, endothelium-dependent relaxant responses to acetylcholine and endothelium-independent relaxant responses to sodium nitroprusside were not affected by RCM-101. However, RCM-101 inhibited relaxations to l-arginine in endothelium-denuded rat aortic preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did not affect leukotriene B4 formation in isolated porcine neutrophils, induced by the calcium ionophore A23187; however, it inhibited prostaglandin E2 and NO production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7 cells).The findings indicate that RCM-101 may have multiple inhibitory actions on the release and/or synthesis of inflammatory mediators involved in allergic rhinitis.

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.

Vasorelaxant Effect of the Rootbark Extract of Paeonia moutan on Isolated Rat Thoracic Aorta

The vascular relaxant effect of the rootbark extract of Paeonia moutan was evaluated in isolated rat thoracic aorta. The methanolic extract of the rootbark showed a vasorelaxant activity in rat aortic preparations precontracted with 0.3 microM phenylephrine (IC50 value: 16.8 microg/mL). The activity-guided fractionation of the extract led to the isolation of five active principles such as paeoniflorin (1), paeonidanin (2), methylpaeoniflorin (4), tetragalloylglucose (5) and pentagalloylglucose (6), and these active ingredients potently relaxed phenylephrine-induced contraction of rat aortic preparations in a concentration-dependent manner (IC50 values: 19.4, 7.9, 10.1, 5.1 and 3.6 microM, respectively). These results suggest that pinane glycosides and galloylglucoses might be the components responsible for the vasorelaxant properties of the rootbark extract of P. moutan, and their vasorelaxant effects may be mediated through increases in the release of nitric oxide from endothelial cells.