scholarly journals Endothelium-Independent Vasodilatory Effect of Sailuotong (SLT) on Rat Isolated Tail Artery

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
S. Y. Yeon ◽  
S. W. Seto ◽  
G. H. H. Chan ◽  
M. Low ◽  
H. Kiat ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Isometric Tension ◽  
Crocus Sativus ◽  
Dependent Manner ◽  
Free Solution ◽  
Concentration Dependent Manner ◽  
Tail Artery ◽  
Wistar Kyoto ◽  
Underlying Mechanisms ◽  
Rat Tail

Background. Sailuotong (SLT) is a standardized three-herb formulation consisting of extracts of Panax ginseng, Ginkgo biloba, and Crocus sativus for the treatment of vascular dementia (VaD). Although SLT has been shown to increase cerebral blood flow, the direct effects of SLT on vascular reactivity have not been explored. This study aims to examine the vasodilatory effects of SLT and the underlying mechanisms in rat isolated tail artery. Methods. Male (250–300 g) Wistar Kyoto (WKY) rat tail artery was isolated for isometric tension measurement. The effects of SLT on the influx of calcium through the cell membrane calcium channels were determined in Ca2+-free solution experiments. Results. SLT (0.1–5,000 μg/ml) caused a concentration-dependent relaxation in rat isolated tail artery precontracted by phenylephrine. In the contraction experiments, SLT (500, 1,000, and 5,000 μg/mL) significantly inhibited phenylephrine (0.001 to 10 μM)- and KCl (10–80 mM)-induced contraction, in a concentration-dependent manner. In Ca2+-free solution, SLT (500, 1,000, and 5,000 μg/mL) markedly suppressed Ca2+-induced (0.001–3 mM) vasoconstriction in a concentration-dependent manner in both phenylephrine (10 μM) or KCl (80 mM) stimulated tail arteries. L-type calcium channel blocker nifedipine (10 μM) inhibited PE-induced contraction. Furthermore, SLT significantly reduced phenylephrine-induced transient vasoconstriction in the rat isolated tail artery. Conclusion. SLT induces relaxation of rat isolated tail artery through endothelium-independent mechanisms. The SLT-induced vasodilatation appeared to be jointly meditated by blockages of extracellular Ca2+ influx via receptor-gated and voltage-gated Ca2+ channels and inhibition of the release of Ca2+ from the sarcoplasmic reticulum.

scholarly journals Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2748 ◽  
Author(s):  
Fernando Romero ◽  
Javier Palacios ◽  
Ignacio Jofré ◽  
Cristian Paz ◽  
Chukwuemeka R. Nwokocha ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Vascular Reactivity ◽  
Soluble Guanylate Cyclase ◽  
Indole Alkaloid ◽  
Soluble Guanylyl Cyclase ◽  
Rat Aorta ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cav1.2 Channels ◽  
Aristotelia Chilensis

Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl2 (Kir), 10 μM glibenclamide (KATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (p < 0.05) reduced the ARI-induced relaxation. ARI significantly (p < 0.05) reduced the contractile response to agonist of CaV1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway.

Mechanism of Cepharanthine Cytotoxicity in Human Ovarian Cancer Cells

Planta Medica ◽  
2018 ◽  
Vol 85 (01) ◽  
pp. 41-47 ◽  
Author(s):  
Vilawan Payon ◽  
Chanaporn Kongsaden ◽  
Wannarasmi Ketchart ◽  
Apiwat Mutirangura ◽  
Piyanuch Wonganan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cell ◽  
Apoptotic Cell ◽  
Chemotherapeutic Agents ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ovarian Cancer Cell Lines ◽  
Underlying Mechanisms

AbstractCepharanthine (CEP), a medicinal product derived from Stephania cephalantha Hayata, possesses a potent cytotoxicity against several types of cancers. Recently, we have found that CEP could efficiently inhibit the growth of mutated p53 colon cancer cells, which are often resistant to commonly used chemotherapeutic agents. In this study, we evaluated the cytotoxic effect and the underlying mechanisms of CEP on both chemosensitive CaOV-3 and chemoresistant OVCAR-3 ovarian cancer cell lines. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a time- and concentration-dependent manner. CEP arrested CaOV-3 and OVCAR-3 cells in the G1 phase and S phase of cell cycle, respectively. Western blot analysis demonstrated that CEP markedly increased the expression of p21Waf1 protein and decreased the expression of cyclins A and D proteins in both CaOV-3 and OVCAR-3 cells. Additionally, CEP triggered apoptotic cell death in OVCAR-3 cells. Taken together, the above results suggest that CEP is a promising anticancer drug for ovarian cancer.

scholarly journals Metformin Alleviated Aβ-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Bin Chen ◽  
Ying Teng ◽  
Xingguang Zhang ◽  
Xiaofeng Lv ◽  
Yanling Yin
Keyword(s):  
P38 Mapk ◽  
Hippocampal Neurons ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ldh Assay ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Positive Effect

Both diabetes and hyperinsulinemia are confirmed risk factors for Alzheimer’s disease. Some researchers proposed that antidiabetic drugs may be used as disease-modifying therapies, such as metformin and thiazolidinediones, although more evidence was poorly supported. The aim of the current study is to investigate the role of metformin in Aβ-induced cytotoxicity and explore the underlying mechanisms. First, the experimental results show that metformin salvaged the neurons exposed to Aβin a concentration-dependent manner with MTT and LDH assay. Further, the phosphorylation levels of JNK, ERK1/2, and p38 MAPK were measured with western blot analysis. It was investigated that Aβincreased phospho-JNK significantly but had no effect on phospho-p38 MAPK and phospho-ERK1/2. Metformin decreased hyperphosphorylated JNK induced by Aβ; however, the protection of metformin against Aβwas blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Aβin a JNK-dependent way. In addition, it was observed that metformin protected the neurons via the suppression of apoptosis. Taken together, our findings demonstrate that metformin may have a positive effect on Aβ-induced cytotoxicity, which provides a preclinical strategy against AD for elders with diabetes.

Three different vasoactive responses of rat tail artery to nicotine

1999 ◽  
Vol 78 (1) ◽  
pp. 20-28
Author(s):  
Rui Wang ◽  
Zunzhe Wang
Keyword(s):  
Smooth Muscles ◽  
Rat Tail Artery ◽  
Vascular Smooth Muscles ◽  
Vascular Effects ◽  
Tail Artery ◽  
Complete Relaxation ◽  
Underlying Mechanisms ◽  
Channel Currents ◽  
Rat Tail ◽  
Isolated Rat

The vasoactive effects of nicotine on isolated rat tail artery tissues were studied. Nicotine transiently contracted rat tail artery tissues (EC50, 55.6 ± 2 µM) in an extracellular Ca2+ dependent and endothelium-independent fashion. The blockade of alpha1-adrenoceptors, but not alpha2-adrenoceptors or P2X purinoceptors, inhibited the nicotine-induced contraction by 38 ± 7% (p < 0.05). Nicotine (1 mM) depolarized membrane by 13 ± 3 mV, but did not affect L-type Ca2+ channel currents, of the isolated rat tail artery smooth muscle cells. The phenylephrine-precontracted tail artery tissues were relaxed by nicotine (EC50, 0.90 ± 0.31 mM), which was significantly inhibited after the blockade of nicotinic receptors. Simultaneous removal of phenylephrine and nicotine, after a complete relaxation of the phenylephrine-precontracted tail artery strips was achieved by nicotine at accumulated concentrations (>=10 mM), triggered a Ca2+-dependent rebound long-lasting vasoconstriction (n = 20). This rebound contraction was abolished in the absence of calcium or in the presence of tetracaine in the bath solution. Pretreatment of vascular tissues with a nicotinic receptor antagonist did not affect the nicotine-induced vasoconstriction or nicotine withdrawal induced rebound contraction. The elucidation of the triphasic vascular effects of nicotine and the underlying mechanisms is important for a better understanding of the complex vascular actions of nicotine.Key words: nicotine, smokeless tobacco, vascular smooth muscles, contraction, relaxation.

Release of endogenous noradrenaline from the rat tail artery induced by veratridine

1982 ◽  
Vol 60 (6) ◽  
pp. 805-810 ◽  
Author(s):  
Vladimír Palatý
Keyword(s):  
Sodium Pump ◽  
Rat Tail Artery ◽  
Free Solution ◽  
Release Of Noradrenaline ◽  
Tail Artery ◽  
Low Concentrations ◽  
Endogenous Noradrenaline ◽  
Increased Activity ◽  
Rat Tail ◽  
Isolated Rat

The overflow of endogenous noradrenaline from the isolated rat tail artery was measured using a radioenzymatic method. Veratridine increased the overflow markedly even in the absence of external Ca2+. Modifications of the effect of 5 μM veratridine by tetrodotoxin, pargyline, cocaine, lidocaine, and phenoxybenzamine indicated that interaction of the alkaloid with the sodium channel induces primarily nonexocytotic release of noradrenaline. Ouabain inhibited the effect of 5 μM veratridine on the overflow into Ca2+ -free solution, but it greatly potentiated the effect if external Ca2+ was present. Potentiation of the effect of veratridine in Ca2+-free solution by cyanide was ouabain sensitive. These observations are consistent with the hypothesis that, at low concentrations of veratridine such as 5 μM, the initial cause of enhanced release of noradrenaline may be a consequence of increased activity of the sodium pump, namely increased consumption of ATP by the pump.

scholarly journals Milrinone inhibits contractility in skinned skeletal muscle fibers

1998 ◽  
Vol 274 (5) ◽  
pp. C1306-C1311 ◽  
Author(s):  
C. Y. Seow ◽  
L. Morishita ◽  
B. H. Bressler
Keyword(s):  
Skeletal Muscle ◽  
Direct Action ◽  
Force Production ◽  
Isometric Tension ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Reduction In Force ◽  
Cross Bridge ◽  
The Cross ◽  
Cross Bridges

Direct action of the cardiotonic bipyridine milrinone on the cross bridges of single fibers of skinned rabbit skeletal muscle was investigated. At 10°C and pH 7.0, milrinone reduced isometric tension in a logarithmically concentration-dependent manner, with a 55% reduction in force at 0.6 mM. Milrinone also reduced Ca2+ sensitivity of skinned fibers in terms of force production; the shift in the force-pCa curve indicated a change in the pCa value at 50% maximal force from 6.10 to 5.94. The unloaded velocity of shortening was reduced by 18% in the presence of 0.6 mM milrinone. Parts of the transient tension response to step change in length were altered by milrinone, so that the test and control transients could not be superimposed. The results indicate that milrinone interferes with the cross-bridge cycle and possibly detains cross bridges in low-force states. The results also suggest that the positive inotropic effect of milrinone on cardiac muscle is probably not due to the drug’s direct action on the muscle cross bridges. The specific and reversible action of the bipyridine on muscle cross bridges makes it a potentially useful tool for probing the chemomechanical cross-bridge cycle.

Comparative cardioprotective effects of cromakalim and diltiazem in ischemic hypertrophied rat hearts

1996 ◽  
Vol 270 (1) ◽  
pp. H174-H182
Author(s):  
G. J. Grover ◽  
S. Dzwonczyk ◽  
T. M. Monticello
Keyword(s):  
Cardiac Hypertrophy ◽  
Contractile Function ◽  
Heart Weight ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Rat Hearts ◽  
Cardioprotective Effects ◽  
Ldh Release ◽  
Wistar Kyoto

Previous studies have indicated that alterations in cardiac ATP-sensitive potassium channels (KATP) can occur with cardiac hypertrophy. The goal of this study was to determine the effect of cardiac hypertrophy in spontaneously hypertensive rats (SHR) on the response to the cardioprotective agents diltiazem and cromakalim. Isolated rat hearts from 14-wk-old SHR, normotensive heterozygote Wistar-Kyoto (WKY), and Sprague-Dawley (SD) strains were subjected to 25 min of global ischemia and 30 min of reperfusion in the presence of vehicle (3-30 microM cromakalim or 0.1-1.0 microM diltiazem). SHR had heart weight-to-body weight ratios 40-50% greater than age-matched SD or WKY. Both diltiazem and cromakalim increased reperfusion contractile function in a concentration-dependent manner in SD rats as previously reported. Cromakalim and diltiazem caused similar improvements in reperfusion function in WKY rats and SHR. Cumulative lactate dehydrogenase (LDH) release during reperfusion was similar for vehicle-treated SD, WKY, or SHR hearts. LDH release was significantly attenuated by cromakalim and dilitiazem at all concentrations tested in SD and WKY hearts, whereas LDH release was not attenuated in SHR hearts by any concentration of cromakalim or diltiazem tested. Morphological assessment of hearts by light microscopy indicated that the severity and distribution of myocardial lesions were not affected by cromakalim in SHR hearts, compared with vehicle-treated SHR, supporting the LDH data. These results suggest that in SHR hearts, cromakalim and dilitiazan may exert much of their cardioprotective effects on the population of myocytes that are not irreversibly damaged.

Analysis of the Mechanisms Underlying the Vasorelaxant Action of Coptisine in Rat Aortic Rings

2012 ◽  
Vol 40 (02) ◽  
pp. 309-320 ◽  
Author(s):  
Li-Li Gong ◽  
Lian-Hua Fang ◽  
Hai-Lin Qin ◽  
Yang Lv ◽  
Guan-Hua Du
Keyword(s):  
Dependent Manner ◽  
Free Solution ◽  
Free Medium ◽  
Response Curves ◽  
Concentration Dependent Manner ◽  
Vasorelaxant Effect ◽  
Voltage Dependent ◽  
Endothelium Dependent Relaxation ◽  
External Calcium ◽  
Isolated Rat

The aim of the present study was to evaluate the vasorelaxant effects of coptisine and its possible mechanisms in isolated rat aortic rings. Coptisine was evaluated on isolated rat aortic rings precontracted with norepinephrine (NE) and KCl. The mechanisms were evaluated in the presence or absence of specific pharmacological inhibitors. Coptisine (1 ~ 200 μM) relaxed NE (1 μM) or KCl (60 mM) induced sustained contraction with pEC50 values of 4.49 ± 0.48 and 4.85 ± 0.57 in a concentration dependent manner. Pretreatment with coptisine (10, 50 or 100 μM) also inhibited concentration-response curves to NE and KCl. The vasorelaxant effect of coptisine was attenuated significantly by endothelium removal, and incubation with Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM), methylene blue (10 μM) and indomethacin (5 μM) partially reduced the vasorelaxant effect of coptisine. In endothelium-denuded rings, the vasorelaxant effect of coptisine was reduced significantly by 4-aminopyridine (4-AP, 100 μM), but not glibenclamide (10 μM) ortetraethylammonium (TEA, 5 mM). Coptisine also reduced NE-induced transient contraction in Ca2+ -free solution, and inhibited contraction induced by increasing external calcium in Ca2+ -free medium plus 60 mM KCl. It was concluded that coptisine induced both endothelium-dependent and -independent relaxation in rat aortic rings. The NO-cGMP mediated pathway may be involved in the endothelium-dependent relaxation and in the activation of voltage-dependent K+ channels, contributing in part to the endothelium-independent relaxation bycoptisine. Coptisine also blocks extracellular Ca2+ influx by interacting with both voltage- and receptor-operated Ca2+ channels.

Vascular Resistance and Na+–K+ Gradients in the Perfused Rat-Tail Artery

1973 ◽  
Vol 51 (6) ◽  
pp. 410-417 ◽  
Author(s):  
S. M. Friedman ◽  
M. Nakashima ◽  
V. Palatý ◽  
B. K. Walters
Keyword(s):  
Vascular Resistance ◽  
Arterial Wall ◽  
Physiological Salt Solution ◽  
Delayed Response ◽  
Rat Tail Artery ◽  
Free Solution ◽  
Experimental Conditions ◽  
Tail Artery ◽  
External Potassium ◽  
Rat Tail

The changes in the resistance of the perfused ventral rat-tail artery resulting from exposure of the tissue to ouabain-containing and/or K+-free physiological salt solution were studied. In each case, there was an increase in the vascular resistance which was not sustained. The response of the arterial wall to the above stimuli was abolished in the absence of external Ca2+. In contrast to the delayed response of the wall to either ouabain-containing or K+-free solution, an almost instantaneous rise in the resistance was observed if the two stimuli were combined, though the rate of loss of the tissue K+ was not accelerated significantly under these experimental conditions. The tension developed in K+-free solution was relieved almost instantaneously upon readmittance of external potassium.

Effect of Volatile Anesthetics with and without Verapamil on Intracellular Activity in Vascular Smooth Muscle

1996 ◽  
Vol 84 (6) ◽  
pp. 1465-1474 ◽  
Author(s):  
Hitoshi Namba ◽  
Hideaki Tsuchida
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Muscle Tension ◽  
Volatile Anesthetics ◽  
Smooth Muscle Contraction ◽  
Isometric Tension ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Pharmacomechanical Coupling ◽  
Intracellular Action

Background Although halothane and isoflurane inhibit receptor agonist-induced smooth muscle contraction by inhibiting Ca2+ influx via the L-type voltage-dependent Ca2+ channels, their effects on pharmacomechanical coupling remained to be clarified. The intracellular action of both anesthetics was studied during agonist-induced contractions using the Ca2+ channel blocker verapamil. Methods Isolated spiral strips of rat thoracic aorta with endothelium removed were suspended for isometric tension recordings in physiologic salt solution. Cytosolic concentration of Ca2+ ([Ca2+]i) was measured concomitantly using fura-2-Ca2+ fluorescence. Muscle contraction was evoked by the receptor agonists with 30 nm norepinephrine or 10 microM prostaglandin F2 alpha (PGF2 alpha), followed by exposure to halothane, at 0%, 1%, 2%, and 3% or isoflurane, at 2% and 4%. The effects of the anesthetics were compared with those of 0.1-1 microM verapamil (n = 8 for each condition). To clarify the intracellular action of the volatile anesthetics on agonist-induced contractions, this procedure was repeated for the anesthetics only in the presence of 1 microM verapamil (n = 8 for each condition). The effects of both anesthetics were also examined in nonreceptor-mediated contractions evoked with a 1-microM dose of the protein kinase C activator, 12-deoxyphorbol 13-isobutylate, which increases the Ca2+ sensitivity of the contractile elements (n = 8 for each). Results Halothane, isoflurane, and verapamil suppressed norepinephrine-and PGF2 alpha-induced increases in muscle tension and [Ca2+]i in a concentration-dependent manner. The Ca2+-tension regression lines suggested that the volatile anesthetics reduced Ca2+ sensitivity of the contractile elements during PGF2 alpha-induced contraction. Pretreatment of the muscle strip with verapamil revealed that halothane and isoflurane released Ca2+ during norepinephrine-induced contraction and that [Ca2+]i-tension relationship was modulated during PGF2 alpha-induced contractions. Halothane at 2% and 3% and isoflurane at 4% suppressed 12-deoxyphorbol 13-isobutylate-induced increases in muscle tension, whereas they enhanced increases in [Ca2+]i, indicating that both anesthetics suppressed Ca2+ sensitivity during 12-deoxyphorbol 13-isobutylate-induced contraction. Conclusions Verapamil pretreatment unmasked the intracellular action of the anesthetics. Halothane and isoflurane influenced pharmacomechanical coupling during agonist-induced contraction.

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