Relaxation Of Rat Thoracic Aorta Research Articles

Effect of Ipomoea hederacea Jacq. methanolic extract on blood pressure and relaxation of rat thoracic aorta: evidence indicated the release of NO and H2S

Effect of Ipomoea hederacea Jacq. methanolic extract on blood pressure and relaxation of rat thoracic aorta: evidence indicated the release of NO and H2S

Lidocaine relaxation in isolated rat aortic rings is enhanced by endothelial removal: possible role of Kv, KATP channels and A2a receptor crosstalk.

BackgroundLidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties. Our aim was to investigate lidocaine’s vasoreactivity properties in intact versus denuded rat thoracic aortic rings, and the effect of inhibitors of nitric oxide (NO), prostenoids, voltage-dependent Kv and KATP channels, membrane Na+/K+ pump, and A2a and A2b receptors.MethodsAortic rings were harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, pH 7.4, 37 °C. The rings were pre-contracted sub-maximally with 0.3 μM norepinephrine (NE), and the effect of increasing lidocaine concentrations was examined. Rings were tested for viability after each experiment with maximally dilating 100 μM papaverine. The drugs 4-aminopyridine (4-AP), glibenclamide, 5-hydroxydecanoate, ouabain, 8-(3-chlorostyryl) caffeine and PSB-0788 were examined.ResultsAll drugs tested had no significant effect on basal tension. Lidocaine relaxation in intact rings was biphasic between 1 and 10 μM (Phase 1) and 10 and 1000 μM (Phase 2). Mechanical removal of the endothelium resulted in further relaxation, and at lower concentrations ring sensitivity (% relaxation per μM lidocaine) significantly increased 3.5 times compared to intact rings. The relaxing factor(s) responsible for enhancing ring relaxation did not appear to be NO- or prostacyclin-dependent, as L-NAME and indomethacin had little or no effect on intact ring relaxation. In denuded rings, lidocaine relaxation was completely abolished by Kv channel inhibition and significantly reduced by antagonists of the MitoKATP channel, and to a lesser extent the SarcKATP channel. Curiously, A2a subtype receptor antagonism significantly inhibited lidocaine relaxation above 100 μM, but not the A2b receptor.ConclusionsWe show that lidocaine relaxation in rat thoracic aorta was biphasic and significantly enhanced by endothelial removal, which did not appear to be NO or prostacyclin dependent. The unknown factor(s) responsible for enhanced relaxation was significantly reduced by Kv inhibition, 5-HD inhibition, and A2a subtype inhibition indicating a potential role for crosstalk in lidocaine’s vasoreactivity.

Vasodilator Effect of Glucagon: Receptorial Crosstalk Among Glucagon, GLP-1, and Receptor for Glucagon and GLP-1.

Glucagon is known for its insulin-antagonist effect in the blood glucose homeostasis, while it also reduces vascular resistance. The mechanism of the vasoactive effect of glucagon has not been studied before; thereby we aimed to investigate the mediators involved in the vasodilatation induced by glucagon. The vasoactive effect of glucagon, insulin, and glucagon-like peptide-1 was studied on isolated rat thoracic aortic rings using a wire myograph. To investigate the mechanism of the vasodilatation caused by glucagon, we determined the role of the receptor for glucagon and the receptor for GLP-1, and studied also the effect of various inhibitors of gasotransmitters, inhibitors of reactive oxygen species formation, NADPH oxidase, prostaglandin synthesis, protein kinases, potassium channels, and an inhibitor of the Na(+)/Ca(2+)-exchanger. Glucagon causes dose-dependent relaxation in the rat thoracic aorta, which is as potent as that of insulin but greater than that of GLP-1 (7-36) amide. Vasodilatation by GLP-1 is partially mediated by the glucagon receptor. The vasodilatation due to glucagon evokes via the glucagon-receptor, but also via the receptor for GLP-1, and it is endothelium-independent. Contribution of gasotransmitters, prostaglandins, the NADPH oxidase enzyme, free radicals, potassium channels, and the Na(+)/Ca(2+)-exchanger is also significant. Glucagon causes dose-dependent relaxation of rat thoracic aorta in vitro, via the receptor for glucagon and the receptor for GLP-1, while the vasodilatation evoked by GLP-1 also evolves partially via the receptor for glucagon, thereby, a possible crosstalk between the 2 hormones and receptors could occur.

High conductance potassium channels activation by acid exposure in rat aorta is endothelium-dependent.

BackgroundWe investigated, previously, the mechanism by which extracellular acidification promotes relaxation in rat thoracic aorta. These studies suggested that extracellular acidosis promotes vasodilation mediated by NO, KATP and SKCa, and maybe other K+ channels in isolated rat thoracic aorta. This study was carried out to investigate the paxilline-mediated hyperpolarization induced by acid exposure.ResultsThe relaxation response to HCl-induced extracellular acidification (7.4–6.5) was measured in rat aortic rings pre-contracted with phenylephrine (PE, 10−6 M). The vascular reactivity experiments were performed in endothelium-intact and denuded rings, in the presence of paxilline (10−6 M), which is an inhibitor of high calcium conductance potassium BKCa channels. In rings with endothelium, paxilline inhibits relaxation, triggered by acidification at all pH values lower than 7.2 and had no effect on rings without endothelium, showing that the activation of BKCa is endothelium-dependent.ConclusionHigh conductance potassium channel activation induced by acid exposure is endothelium-dependent.

Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production

BackgroundIt has been reported that GLP-1 agonist exenatide (exendin-4) decreases blood pressure. The dose-dependent vasodilator effect of exendin-4 has previously been demonstrated, although the precise mechanism is not thoroughly described. Here we have aimed to provide in vitro evidence for the hypothesis that exenatide may decrease central (aortic) blood pressure involving three gasotransmitters, namely nitric oxide (NO) carbon monoxide (CO), and hydrogen sulphide (H2S).MethodsWe determined the vasoactive effect of exenatide on isolated thoracic aortic rings of adult rats. Two millimetre-long vessel segments were placed in a wire myograph and preincubated with inhibitors of the enzymes producing the three gasotransmitters, with inhibitors of reactive oxygen species formation, prostaglandin synthesis, inhibitors of protein kinases, potassium channels or with an inhibitor of the Na+/Ca2+-exchanger.ResultsExenatide caused dose-dependent relaxation of rat thoracic aorta, which was evoked via the GLP-1 receptor and was mediated mainly by H2S but also by NO and CO. Prostaglandins and superoxide free radical also play a part in the relaxation. Inhibition of soluble guanylyl cyclase significantly diminished vasorelaxation. We found that ATP-sensitive-, voltage-gated- and calcium-activated large-conductance potassium channels are also involved in the vasodilation, but that seemingly the inhibition of the KCNQ-type voltage-gated potassium channels resulted in the most remarkable decrease in the rate of vasorelaxation. Inhibition of the Na+/Ca2+-exchanger abolished most of the vasodilation.ConclusionsExenatide induces vasodilation in rat thoracic aorta with the contribution of all three gasotransmitters. We provide in vitro evidence for the potential ability of exenatide to lower central (aortic) blood pressure, which could have relevant clinical importance.

Bitter tastants induce relaxation of rat thoracic aorta precontracted with high K+

It has been reported that bitter tastants decrease blood pressure and relax precontracted vascular smooth muscle. However, the underlying mechanisms remain unclear. The aim of the present study was to determine the mechanism underlying the vasorelaxant effect of the bitter tastants. Thoracic aortic rings were isolated from Wistar rats and contractions were measured using an isometric myograph. Intracellular Ca(2+) ([Ca(2+)]i) in single rat thoracic aortic smooth muscle cells was recorded by calcium imaging. Calcium currents in single cells were recorded using patch-clamp techniques. High K(+) (140 mmol/L) induced contractions in rat thoracic aortic rings that were inhibited by 3 mmol/L chloroquine, 3 mmol/L denatonium and 10 μmol/L nifedipine. In single rat thoracic aortic smooth muscle cells, high K(+) increased [Ca(2+)]i and this effect was also blocked by 3 mmol/L chloroquine and 10 μmol/L nifedipine. Under Ca(2+) -free conditions, high K(+) failed to induce contractions in rat thoracic aortic rings. On its own, chloroquine had no effect on the muscle tension of rat aortic rings and [Ca(2+) ]i. The vasorelaxant effects of chloroquine on precontracted rat thoracic aortic rings were not altered by either 1 μg/mL pertussis toxin (PTX), an inhibitor of Gαo/i-protein, or 1 mmol/L gallein, an inhibitor of Gβγ-protein. The results of patch-clamp analysis in single cells indicate that 1 mmol/L chloroquine blocks voltage-dependent L-type Ca(2+) channel (VDLCC) currents from both extracellular and intracellular sides. Together, the results indicate that chloroquine can block VDLCC, independent of PTX- and gallein-sensitive G-proteins, resulting in relaxation of high K(+)-precontracted thoracic aortic smooth muscle.

250 MODULATION OF AORTIC INWARD RECTIFIER POTASSIUM2.1 CHANNEL ACTIVITY BY SULFUR DIOXIDE

The aim of the present work was to study the role of inward rectifier potassium (KIR) channels in mediating relaxation of rat thoracic aorta, and the activity of KIR2.1 channel expressed in Xenopus oocytes in response to sulfur dioxide (SO2) derivatives 1:3 M/M sodium bisulfite (NaHSO3) and sodium sulfite (Na2SO3) PowerLab tissue bath system and two-electrode voltage-clamp technique. SO2 derivatives (3–9 mM)-induced relaxation in aortic rings was inhibited by BaCl2 with IC50 from 6.21 mM to 7 mM and maximum relaxation (Emax) was reduced from 62.026 ±6.527 to 36.085±9.382%. Application of SO2 derivatives (3mM), caused a marked increment in initial and steady state KIR2.1 currents by 54.55% and 60.74%, respectively. Furthermore, addition of barium ion (Ba+2; 100 µM) significantly inhibited initial and steady state KIR2.1 currents by 51.91% and 73.19%, while, when combined with SO2 significantly caused a decrement only in KIR2.1 steady state currents by 69.2% at 5mM-K+ concentration. In the current-voltage relationship experiments, SO2 derivatives demonstrated a stronger rectification of KIR2.1 current in a testing potential -100mV, when the currents were evoked by repolarizing pulses from holding to test potentials (+60 to -100 mV) in 20 mV decrement. SO2 failed to change KIR2.1 channel chord conductance calculated from current-voltage relationship from current values of the voltages between –60 mV and -100 mV in both K+ concentrations 5 mM and 30 mM. On the other hand, application of Ba+2 and their combination with SO2 markedly attenuated KIR2.1 currents in voltages between –80 to –100mV and chord conductance. These results provide the first evidence for activation of KIR2.1 channel by SO2 derivatives, and the stimulatory effect of SO2 derivatives is voltage-dependent.

Endothelium derived relaxation factors reduce sulfur dioxide-induced aortic relaxation

The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation of rat thoracic aorta, in response to sulfur dioxide (SO2) derivatives “1:3 M/M sodium bisulfite (NaHSO3) and sodium sulfite (Na2SO3)” using PowerLab tissue bath system. Endothelial denudation enhanced relaxation responses of SO2 derivatives with an IC50 of 6.11 mM as compared to control rings with an IC50 of 6.21 mM, as well as the maximum relaxation (Emax) was increased from 62.026% ± 6.527% to 83.13% ± 14.755%. Furthermore, the relaxation responses to SO2 derivatives in aortic rings were significantly enhanced by indomethacin, clotrimazole and methylene blue with IC50’s of 4.8 mM, 5.33 mM and 4.01 mM, and Emax were raised to 101.1% ± 6.537%, 66.92 ± 7.538 and 104.68 ± 3.575, respectively. Meanwhile, L-NAME did not alter dose-dependent relaxation of SO2 derivatives in comparison to control aortic rings. The results of this study had shown that endothelium denudation and blocking of endothelium derived-relaxation factors enhanced vasodilator effect of SO2; this may clarify the role of endothelium in the vasodilatory mechanism of SO2.

Relaxation of rat thoracic aorta by fibrate drugs correlates with their potency to disturb intracellular calcium of VSMCs

Phenotypic modifications of vascular smooth muscle cells (VSMCs) contribute to pathological changes in atherosclerosis where modulation of intracellular calcium plays an important role. In this study, three fibrate drugs, namely gemfibrozil (Gem), fenofibric acid (Fa) and bezafibrate (Beza), were revealed to relax thoracic aorta associated with their potency to reduce intracellular calcium ([Ca2+]i) in cultured VSMCs. Relaxation effect of Gem, Fa and Beza was assayed on precontracted rat aortic rings. [Ca2+]i level in VSMCs following addition of these fibrates was measured by laser scanning confocal microscopy or flow cytometry. Resultantly, three fibrates showed activity for vasodilation with potency order of Gem>Fa>Beza. Sustained potent reduction of [Ca2+]i was observed with Gem 50mg/L and mild reduction with Fa 400–600mg/L, while no effect had been detected for Beza under our current system. Thus, the potency of these fibrates to relax aortic rings correlate well with their effect on [Ca2+]i reduction, strongly implicating an underlying causal relationship. Considering that Gem potently reduces [Ca2+]i in its clinical concentration range, this study suggests an insight to in situ pharmacological effects of anti-atherosclerosis and clinical toxicity risk.

Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta

We investigated the mechanism by which extracellular acidification promotes relaxation in rat thoracic aorta. The relaxation response to HCl-induced extracellular acidification (7.4 to 6.5) was measured in aortic rings pre-contracted with phenylephrine (Phe, 10−6 M) or KCl (45mM). The vascular reactivity experiments were performed in endothelium-intact and denuded rings, in the presence or absence of indomethacin (10−5 M), L-NAME (10−4 M), apamin (10−6 M), and glibenclamide (10−5 M). The effect of extracellular acidosis (pH 7.0 and 6.5) on nitric oxide (NO) production was evaluated in isolated endothelial cells loaded with diaminofluorescein-FM diacetate (DAF-FM DA, 5μM). The extracellular acidosis failed to induce any changes in the vascular tone of aortic rings pre-contracted with KCl, however, it caused endothelium-dependent and independent relaxation in rings pre-contracted with Phe. This acidosis induced-relaxation was inhibited by L-NAME, apamin, and glibenclamide, but not by indomethacin. The acidosis (pH 7.0 and 6.5) also promoted a time-dependent increase in the NO production by the isolated endothelial cells. These results suggest that extracellular acidosis promotes vasodilation mediated by NO, KATP and SKCa, and maybe other K+ channels in isolated rat thoracic aorta.

Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta.

Reactive oxygen species (ROS) are produced in different metabolic processes including the respiratory burst of neutrophils accompanying local inflammation. The aim of this study was to analyze the effects of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated neutrophils, isolated from the guinea pig peritoneal cavity, on isolated rings of a large (conduit) artery, the rat thoracic aorta. FMLP-activated neutrophils enhanced the basal tension increased by α1-adrenergic stimulation. In phenylephrine-precontracted aortae, they elicited marked contraction, while in noradrenaline-precontracted rat aortal rings they caused a biphasic response (contraction-relaxation). To eliminate interaction of activated neutrophils with catecholamines, in the subsequent experiments the basal tension was increased by KCl-induced depolarization. Activated neutrophils evoked a low-amplitude biphasic response (relaxation-contraction) on the KCl-induced contraction. Not only the acetylcholine- and A23187-induced relaxations but also the catalase sensitive hydrogen peroxide (H2O2) elicited contractions were endothelium-dependent. Even though the acetylcholine-induced relaxation was changed by activated neutrophils and by the ROS studied, their effects differed significantly, yet none of them did eliminate fully the endothelium-dependent acetylcholine relaxation. The effect of activated neutrophils resembled the effect of superoxide anion radical (O2 •–) produced by xanthine/xanthine oxidase (X/XO) and differed from the inhibitory effects of Fe2SO4/H2O2-produced hydroxyl radical (•OH) and H2O2. Thus O2 •– produced either by activated neutrophils or X/XO affected much less the endothelium-dependent acetylcholine-activated relaxation mechanisms than did •OH and H2O2. In the large (conduit) artery, the effects of activated neutrophils and various ROS (O2 •–, •OH and H2O2) seem to be more dependent on muscle tension than on endothelial mechanisms.

Extracellular alkalinization induces endothelium-derived nitric oxide dependent relaxation in rat thoracic aorta

Aim To investigate the mechanism through which the extracellular alkalinization promotes relaxation in rat thoracic aorta. Methods The relaxation response to NaOH-induced extracellular alkalinization (7.4–8.5) was measured in aortic rings pre-contracted with phenylephrine (Phe, 10 −6 M). The vascular reactivity experiments were performed in endothelium-intact and -denuded rings, in the presence or and absence of indomethacin (10 −5 M), NG-nitro- l-arginine methyl ester (L-NAME, 10 −4 M), N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide/HCl (W-7, 10 −7 M), 2,5-dimethylbenzimidazole (DMB, 2 × 10 −5 M) and methyl-β-cyclodextrin (10 −2 M). In addition, the effects of NaOH-induced extracellular alkalinization (pH 8.0 and 8.5) on the intracellular nitric oxide (NO) concentration was evaluated in isolated endothelial cells loaded with diaminofluorescein-FM diacetate (DAF-FM DA, 5 μM), in the presence and absence of DMB (2 × 10 −5 M). Results The extracellular alkalinization failed to induce any change in vascular tone in aortic rings pre-contracted with KCl. In rings pre-contracted with Phe, the extracellular alkalinization caused relaxation in the endothelium-intact rings only, and this relaxation was maintained after cyclooxygenase inhibition; completely abolished by the inhibition of nitric oxide synthase (NOS), Ca 2+/calmodulin and Na +/Ca 2+ exchanger (NCX), and partially blunted by the caveolae disassembly. Conclusions These results suggest that, in rat thoracic aorta, that extracellular alkalinization with NaOH activates the NCX reverse mode of endothelial cells in rat thoracic aorta, thereby the intracellular Ca 2+ concentration and activating the Ca 2+/calmodulin-dependent NOS. In turn, NO is released promoting relaxation.

Endothelium-dependent sensory non-adrenergic non-cholinergic vasodilatation in rat thoracic aorta: involvement of ATP and a role for NO.

The involvement of non-adrenergic non-cholinergic (NANC) transmitters, such as adenosine 5'-triphosphate (ATP) and nitric oxide (NO), in the neurogenic relaxation of rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to electrical field stimulation (EFS) and exogenous vasodilator were investigated in vessels precontracted with 5-hydroxytryptamine. EFS (100 V, 2-16 Hz, for 10 s at 3-min intervals), in the presence of guanethidine (10 microM) and atropine (10 microM) produced frequency-dependent relaxations. Pretreatment with tetrodotoxin (1 microM) markedly reduced the relaxation and desensitization with capsaicin (10 microM) significantly inhibited the relaxation. Exogenously added ATP caused concentration-dependent relaxations. Mechanical removal of the endothelium significantly inhibited EFS- and ATP-induced relaxation by 30+/-3% and 37+/-2%, respectively. Pretreatment with a P1-purinoceptor antagonist, 8-phenyltheophylline (10 microM) or P2X-purinoceptor antagonist, Evans blue (10 microM) did not influence the relaxations to EFS and exogenously added ATP. In contrast, the P2Y-purinoceptor antagonist, basilen blue (100 microM) markedly reduced the relaxations to EFS by 52+/-4% in the endothelium-intact preparations. However, in the endothelium-denuded preparations and capsaicin-pretreated preparations, basilen blue did not change relaxations elicited by EFS. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM) also significantly inhibited the relaxations to EFS and ATP by 40+/-6% and 30+/-2%, respectively, in the endothelium-intact preparations but had no effect on the relaxations in the endothelium-denuded preparations or capsaicin-pretreated preparations. In addition, the EFS-induced relaxations were also inhibited 43+/-7% by pretreatment with 1H-[1,2,4]-oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ; 1 microM), soluble guanylate cyclase inhibitor. This study suggests that the NANC nerve system is present in the thoracic aorta of rat, mediating vasodilatation by sensory nerves. ATP, as a neurotransmitter released from sensory nerves, activates P2Y-purinoceptors located on the endothelium and stimulates the NO/cyclic GMP pathway, resulting in vasodilatation.

Gomisin A induces Ca 2+-dependent activation of eNOS in human coronary artery endothelial cells

Aim of the study Gomisin A (GA) is a small molecular weight lignan contained in Fructus Schisandrae, the dried seed of Schisandra chinensis which is widely used as a tonic in traditional Korean medicine. We previously demonstrated that GA induces endothelium-dependent and -independent relaxation in rat thoracic aorta, however the signaling pathways involved was not clarified. In this study, we examined whether GA could actually induce nitric oxide (NO) production and clarified the mechanism in cultured human coronary artery endothelial cells (HCAEC). Results Treatment of HCAEC with GA induced NO production in a time- and concentration-dependent manner in association with an enhanced endothelial NO synthase (eNOS) activity with an increased cytosolic translocation of eNOS. Both GA-induced NO production and eNOS activation were attenuated by pretreatment of the cells with EGTA, an extracellular Ca 2+ chelator, and BAPTA-AM, an intracellular Ca 2+ chelator, but not by LY 294002, a PI3-kinase/Akt inhibitor, suggesting involvement of Ca 2+. Furthermore, GA rapidly increased the intracellular Ca 2+ concentration, which was abolished in Ca 2+ free media. Conclusion Taken together, our results suggest that GA induces Ca 2+-dependent activation and translocation of eNOS in HCAEC, events linked to NO production and thereby endothelial-dependent vasorelaxation.

Rat thoracic aorta and mesenteric artery show a multiphasic contraction‐relaxation‐contraction response to sodium sulfide and sodium hydrosulfide

Hydrogen sulfide (H2S) is now a recognized gas signaling molecule in the cardiovascular system, joining nitric oxide and carbon monoxide. H2S has been shown to cause relaxation in rat thoracic aorta (TA) and mesenteric artery (MA), as well as multiphasic responses in pulmonary artery and other vertebrate vessels. While relaxation occurs shortly after H2S addition, multiphasic responses require more time to observe. Therefore in this study, we hypothesized that TA and MA would show a multiphasic response to H2S if time were allowed for completion. TA and MA were dissected from Fisher 344 x Brown Norway rats. TA was sectioned into rings and run on a wire myograph, and MA was run on a pressure arteriograph. H2S was added via the donors sodium sulfide (Na2S) or sodium hydrosulfide (NaHS) after preconstriction with phenylephrine. Both TA and MA showed a triphasic contraction‐relaxation‐contraction response using either H2S donor. The first contraction was quick and small in magnitude. A sustained relaxation followed, after which a second sustained contraction much larger in magnitude than the first occurred. Overall the triphasic response was complete in 15‐30 min. These data show that H2S signaling in mammalian vessels is more complex than a monophasic relaxation, regardless of the H2S donor, and therefore the entire mulitphasic response to H2S should be considered when investigating potential H2S signaling mechanisms.

Endothelin ETBReceptors in Arteries and Veins: Multiple Actions in the Vein

Endothelin receptors (ET(A) and ET(B)) mediate responses to ET-1. ET(B) receptor function seems to differ between a similarly sized arterial and venous pair, the rat vena cava (RVC) and rat thoracic aorta (RA). ET(B) receptors mediate RVC contraction directly, but it is unclear whether ET(B) receptors mediate contraction in RA. Because of these apparent differences in ET(B) receptor-mediated vascular contraction, we hypothesize that relaxant ET(B)-receptor mechanisms in RVC would be different from those in RA. RA and RVC rings were isolated from rats for measurement of isometric contraction. When contracted with prostaglandin F-2alpha (PGF-2alpha) (20 microM), the ET(B) receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. N(omega)-Nitro-L-arginine (LNNA) (100 microM) or endothelial denudation abolished relaxation to S6c in RA. By contrast, S6c-induced relaxation of RVC was attenuated but not abolished by LNNA and endothelial denudation. RVC (PGF-2alpha-contracted) relaxed to low concentrations of ET-1, whereas under the same conditions RA responded with contraction. ET-1-induced relaxation in RA was observed only with ET(A) receptor blockade. Vessels from dopamine-beta-hydroxylase-ET(B) transgenic rats, which lack functional ET(B) receptors in the vasculature, were also used. RVC (PGF-2alpha-contracted) from these rats did not relax to ET-1. Thus, although both RA and RVC possess endothelial relaxant ET(B) receptors, RA and RVC differ in that relaxant ET(B) receptors may also be present in smooth muscle of RVC. Moreover, the mechanisms of endothelial cell ET(B) receptor-mediated relaxation in RA and RVC are not the same.

Alcohol Induces Relaxation of Rat Thoracic Aorta and Mesenteric Arterial Bed

The aim of this study was to investigate the effect of alcohol on rat artery and its underlying mechanism. The tension of isolated Sprague-Dawley rat thoracic aortic rings and the pressure of rat mesenteric arterial beds perfused with different concentrations of alcohol (0.1-7.0 per thousand) were measured. At resting tensions, alcohol caused a concentration-dependent relaxation on endothelium-denuded aortic rings precontracted with KCl (6 x 10(-2) mol/L) or phenylephrine (PE, 10(-6) mol/L), and this effect was most evident on rings at a resting tension of 3 g. Alcohol induced much less vasodilation on endothelium-intact rings. Alcohol inhibited the CaCl(2)-induced contraction of endothelium-denuded aortic rings precontracted with KCl or PE. Incubation of rings with dantrolene (5 x 10(-5) mol/L), a ryanodine receptor blocker, or 2-aminoethyl diphenylborinate (7.5 x 10(-5) mol/L), an IP(3) receptor blocker, attenuated the vasodilating effect of alcohol on rings precontracted with PE. Alcohol also concentration-dependently relaxed rat mesenteric arterial beds precontracted with KCl (6 x 10(-2) mol/L) or PE (10(-5) mol/L), which was more potent on endothelium-denuded than on endothelium-intact beds. Alcohol has a vasodilating effect on rat artery depending on the resting tension. Both extracellular and intracellular Ca(2+) mobilization of vascular smooth muscle cells are involved in the vascular effect of alcohol.

Study on Vasorelaxant Mechanism induced by Extract of Zanthoxylium piperitum Leaves

A methanol extract of Zanthoxylium piperitum (MZP) Leaves relaxed vascular smooth muscle in rats. Therefore, the aim of the present study was to define the mechanism of the MZP‐induced vascular relaxation in rat thoracic aorta. Among the four solvent partitions of MZP, n‐butanol (BZP) and water extract (WZP) of Zanthoxylium piperitum Leaves induced relaxation of the phenylephrine‐precontracted rat aorta in a dose‐dependent manner, respectively, and its effects were both abolished by the removal of functional endothelium. Pretreatment of the endothelium‐intact aortic tissues with NG‐nitro‐L‐arginine methyl ester (L‐NAME) and 1H‐[1,2,4]‐oxadiazole‐[4,3‐α]‐quinoxalin‐1‐one (ODQ) inhibited the relaxation induced by BZP and WZP, respectively. On the other hand, vascular relaxation induced by BZP or WZP were not blocked by several inhibitors including indomethacin, atropine, propranolol, tetraethylammonium (TEA), glibenclamide, verapamil, and diltiazem, respectively. In addition, phenylephrine or epinephrine‐induced aortic contraction was also blocked by treated with BZP and WZP, respectively. These results suggest that BZP and WZP dilate vascular smooth muscle via endothelium‐dependent nitric oxide/cGMP signaling pathway.

Ethanol induced relaxation of rat thoracic aorta at different resting tension and its possible mechanism

The aim of this study was to investigate the vascular effect of ethanol on rat aorta at different resting tension and its underlying mechanism. The tension of the isolated Sprague-Dawley rat thoracic aortic rings perfused with different concentrations of ethanol was measured using organ bath technique. At different resting tension (1.0 – 4.0 g), ethanol (0.1 – 7.0 ‰) caused a concentration-dependent relaxation on endothelium-denuded aortic rings precontracted with KCl (6×10−2 mol/L) or phenylephrine (PE, 10−6 mol/L), and the vasodilating effect was the most potent when the aortic rings was at the resting tension of 3 g. Ethanol inhibited the CaCl2 induced contraction and downward shifted concentration-response curve of endothelium-denuded aortic rings precontracted with KCl or PE. Incubation of aorta with ruthenium red (10−5 mol/L) or heparin (50 mg/L) decreased the vasodilating effect of ethanol. The results indicate that endothelium-independent relaxation induced by ethanol is concerned with the resting tension. This effect of ethanol may be mediated by the inhibition of voltage-dependent and receptor-operated Ca2+ channels in the vascular smooth muscle cells as well as the inhibition of the intracellular ryanodine receptor and IP3 pathway. (Supported by the National Natural Science Foundation for Fostering Talents in Basic Science, No. J0530183)

Treatment of interferon-alpha in reducing the endothelium-dependent relaxation of rat thoracic aorta

To investigate the vascular effect of acute and chronic treatment of interferon-alpha (IFN-alpha) in rat aortic rings. Isolated thoracic aortic rings were mounted on the organ bath and the tension of the vessel was recorded. IFN-alpha(10, 100, 1,000 and 10,000 U/ml) caused concentration -dependent relaxation of endothelium-intact aorta rings preconstricted with phenylephrine (PE,10(-6)mol/L), to(90.1+/-0.91)%, (65.1+/-5.21)%, (39.5+/-8.22)% and (35.3+/-8.27)% of pre-drug control, respectively. Removal of the endothelium inhibited the relaxation by IFN-alpha. The vasorelaxant effect of IFN-alpha (100 U/ml ) was attenuated by pretreatment with L-NAME (10(-4)mol/L), methylene blue (10(-5)mol/L) or AMG (10(-4)mol/L), to (97.2+/-5.34)%, (95.1+/-6.25)% and (93.7+/-8.82)% of the control, respectively. Pretreatment with IFN-alpha (1,000,000 U/d, i.p.) for five days markedly inhibited the endothelium-dependent relaxation of the aortic rings to acetylcholine. But the endothelium-dependent relaxation to acetylcholine was not changed by pretreatment of IFN-alpha (10,000 U/ml) with the isolated aorta rings for 2 h. The vasorelaxation induced by IFN-alpha in rat aorta rings is endothelium-dependent and is possibly mediated by inducible nitric oxide synthase. Chronic treatment of IFN-alpha may impair the endothelium or NO-sGC pathway.