1.Effect of vasonatrin peptide on the Ca2+ activated K+ channels of vascular smooth muscle cells isolated from rat mesentery arteries.
Jun YU ; Miao-Zhang ZHU ; Li-Bing LIU ; Bao-Ying CHEN ; Shun-Yan LU ; Jing-Jun ZHOU ; Zhao-Jun FU
Chinese Journal of Applied Physiology 2006;22(1):94-97
AIMTo investigate effect and mechanism of vasonatrin peptide (VNP) on Ca2+ activated K+ channels (K(Ca)) of vascular smooth muscle cells (VSMCs) isolated from rat mesentery arteries.
METHODSChanges of K(Ca) induced by VNP were measured by the means of whole cell recording mode of patch clamp, furthermore effects of HS-142-1(0.3 g/L), 8-Br-cGMP and methylene blue (MB) were observed.
RESULTSK(Ca) was significantly enhanced by VNP (10(-6) mol/L), which was mimicked by 8-Br-cGMP(10(-3) mol/L) and blocked completely by HS-142-1 or MB (2 x 10(-5) mol/L).
CONCLUSIONVNP increases K(Ca) of VSMCs isolated from rat mesenteric arteries, by binding with natriuretic peptide guanylate cyclase-coupled receptors and increasing the intracellular level of cGMP in VSMCs.
Animals ; Atrial Natriuretic Factor ; pharmacology ; Male ; Mesenteric Arteries ; cytology ; drug effects ; metabolism ; Muscle, Smooth, Vascular ; metabolism ; physiology ; Potassium Channels, Calcium-Activated ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley
2.Vasodilating effect of capsaicin on rat mesenteric artery and its mechanism.
Qiang CHEN ; Huanhuan ZHU ; Yuanyuan ZHANG ; Yuan ZHANG ; Lihong WANG ; Liangrong ZHENG
Journal of Zhejiang University. Medical sciences 2013;42(2):177-183
OBJECTIVETo investigate the vasodilating effect of capsaicin (CAP) on rat mesenteric artery and its mechanism.
METHODSThe third branch of the superior mesenteric artery in male Sprague-Dawley rat (250-350 g) was excised, the periadventitial fat and connective tissue were removed and the mesenteric artery was dissected into 2 mm rings. Each ring was placed in a 5 ml organ bath of DMT 610M system and the tension was recorded.
RESULTSCAP (10(-9)-10(-5) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine (10(-5) mol/L), and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Pretreatment with either L-NAME (3 X10(-4) mol/L), an inhibitor of nitric oxide synthase(NOS), or CGRP8-37 (2 X 10(-6) mol/L), an antagonist of calcitonin gene-related peptide (CGRP), for 30 min significantly attenuated the relaxation of endothelium-intact mesenteric artery induced by CAP. CGRP (10(-10)-3 X10(-8) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine, and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Substance P did not relax the mesenteric artery pre-constricted by phenylephrine.
CONCLUSIONCAP has partial endothelium-dependent relaxation effect on rat mesenteric artery, which may be mediated by activating the endothelial NOS-NO pathway. The endothelium-independent relaxation in rat mesenteric artery induced by CAP may be mediated by CGRP.
Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Capsaicin ; pharmacology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Peptide Fragments ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects
3.Study on vasorelaxations of oxyphenamone and its mechanism.
Acta Pharmaceutica Sinica 2002;37(1):10-13
AIMTo study the vasorelaxation action of oxyphenamone (Oxy) and its mechanism.
METHODSThe contractile response of isolated rabbit renal, femoral and mesentery artery preparations was determined.
RESULTSOxy was shown to inhibit the contractile force of renal, femoral and mesentery arteries induced by phenylephrine in a concentration dependent manner. The vasorelaxation produced by Oxy was not attenuated by removal of the endothelium. Oxy (10(-6)-10(-4) mol.L-1) relaxed the contractions induced by KCl 30 mmol.L-1 as well as KCl 80 mmol.L-1, but the contraction curve of KCl 80 mmol.L-1 was shifted significantly to the right. Oxy in lower concentration (10(-6) and 5 x 10(-6) mol.L-1) increased the contractions induced by Ang II, and in middle concentration (10(-5) mol.L-1) it did not affect the contractions induced by Ang II. Whereas in higher concentration (5 x 10(-5) mol.L-1) it obviously inhibited the contractions induced by Ang II.
CONCLUSIONOxy showed significant vasorelaxation to various vascular preparations, and its vasorelaxation action is endothelium independent. The mechanism of its vasorelaxations seems to be related with Ca2+ activated K+ channel (Kca channel) and Ca2+ channel in vascular smooth muscle cells but its true mechanism needs further study.
Animals ; Cardiotonic Agents ; pharmacology ; Female ; Femoral Artery ; drug effects ; physiology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Organic Chemicals ; Phenylephrine ; antagonists & inhibitors ; Potassium Channels, Calcium-Activated ; metabolism ; Rabbits ; Renal Artery ; drug effects ; physiology ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology
4.Effect and mechanism of Danhong injection on isolated mesenteric arterial rings in rats.
Xiao-wen ZHI ; Xian-ming SU ; Wei-yi FENG ; Hong-mei ZHANG
China Journal of Chinese Materia Medica 2012;37(17):2607-2611
OBJECTIVETo study the effect and mechanism of Danhong injection on isolated mesenteric arterial rings in rats.
METHODAn isolated vascular ring experiment was conducted to determine the changes in tension of vascular rings with a biological signal collection and analytical system.
RESULTDanhong injection had no impact on the tension of vascular rings. Danhong injection showed a significant vasodilatation effect on treated arteria rings of norepinephrine, and no remarkable impact was made on the effect without endothium. It showed notable effect on blood vessels treated with Ca(2+) and no significant impact on those treated with caffeine. It could inhibit NE-induced intracellular calcium from releasing and external calcium from inflowing. No effects of potassium channel blockers on aorta ring tensile force were found.
CONCLUSIONDanhong injection shows significant vasodilation effect, which mainly works through vascular smooth muscle. Its vasodilation effect may be related to inhibitory receptor, voltage-dependent Ca(2+)-release and IP3 receptor-mediated Ca(2 +)-influx.
Animals ; Calcium ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; In Vitro Techniques ; Injections ; Mesenteric Arteries ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects
5.Changes in voltage-dependent calcium channel currents of vascular smooth muscle cells isolated from small mesenteric arteries of simulated weightless rats.
Zhao-Jun FU ; Li-Fan ZHANG ; Jin MA ; Hong-Wei CHENG
Acta Physiologica Sinica 2005;57(1):27-32
The aim of the present study was to examine the changes in the function of voltage-dependent calcium channels (VDC) of vascular smooth muscle cells (VSMCs) isolated from small mesenteric arteries of rats subjected to 1-week or 4-week simulated weightlessness. The whole-cell recording mode was used to record current densities and Ba(2+) was used as charge carrier. Curves and fitting parameters describing steady-state activation and inactivation characteristics of VDC were thus obtained. The inward currents recorded from the VSMCs of small mesenteric arteries were mainly the Ba(2+) currents through the long-lasting type VDC (L-VDC). Compared with that of the control rats, the L-VDC current density of VSMCs from small mesenteric arteries showed a trend toward a decrease in the rats after 1-week , while a significant decrease was observed in the rats after 4-week simulated weightlessness. However, there were no significant differences in the opening and closing rates of L-VDCs, the position of steady-state activation and inactivation curves, and in the parameters, V(0.5) and k, between either of the two groups and its respective control group. The membrane capacitance and the reversal potential of the VSMCs from the small mesenteric arteries of rats after simulated weightlessness also showed no significant changes. These findings suggest that the decreased function of the L-VDC in hindquarter VSMCs might be one of the electrophysiological mechanisms that mediate the depressed vasoreactivity and atrophic change in hindquarter arteries during adaptation to simulated weightlessness in rats.
Animals
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Calcium Channels
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physiology
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Hindlimb Suspension
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Male
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Membrane Potentials
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drug effects
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physiology
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Mesenteric Arteries
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cytology
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physiology
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Muscle, Smooth, Vascular
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cytology
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metabolism
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physiology
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Patch-Clamp Techniques
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Rats
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Rats, Sprague-Dawley
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Weightlessness Simulation
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methods
6.Paeonol induces vasodilatation in rat mesenteric artery via inhibiting extracellular Ca²⁺ influx and intracellular Ca²⁺ release.
Jin-Yan ZHANG ; Yong-Xiao CAO ; Wei-Liang WENG ; Yi-Kui LI ; Le ZHAO
Chinese journal of integrative medicine 2013;19(7):510-516
OBJECTIVETo investigate the vasodilative effect of paeonol in rat mesenteric artery and the mechanisms responsible for it.
METHODSRats were anaesthetized and sacrificed. The superior mesenteric artery was removed, dissected free of adherent tissue and cut into 2.0 mm long cylindrical segments. Isometric tension of artery rings was recorded by a myograph system in vitro. Concentration-relaxation curves of paeonol (17.8 μ mol/L to 3.16 mmol/L) were recorded on artery rings precontracted by potassium chloride (KCl) and concentration-contraction curves of KCl, 5-hydroxytryptamine (5-HT), noradrenaline (NA) or calcium chloride (CaCl2) were recorded in the presence of paeonol (10(-4.5), 10(-3.8), 10(-3.5) mol/L) respectively. And also, concentration-relaxation curves of paeonol were recorded in the presence of different potassium channel inhibitors and propranolol on rings precontracted with KCl respectively. To investigate the role of intracellular Ca(2+) release from Ca(2+) store, the contraction induced by NA (100 μ mol/L) and CaCl2 (2 mmol/L) in Ca(2+) free medium was observed in the presence of paeonol respectively.
RESULTSPaeonol relaxed artery rings precontracted by KCl in a concentration-dependent manner and the vasodilatation effect was not affected by endothelium denudation. Paeonol significant decreased the maximum contractions (Emax) induced by KCl, CaCl2, NA and 5-HT, as well as Emax induced by NA and CaCl2 in Ca(2+) -free medium, suggesting that paeonol dilated the artery via inhibiting the extracellular Ca(2+) influx mediated by voltage-dependent calcium channel, and receptor-mediated Ca(2+)-influx and release. Moreover, none of glibenclamide, tetraethylammonium, barium chlorded and propranolol affected the paeonol-induced vasodilatation, indicating that the vasodilatation was not contributed to ATP sensitive potassium channel, calcium-activated potassium channel, inwardly rectifying potassium channel, and β-adrenoceptor.
CONCLUSIONPaeonol induces non-endothelium dependent-vasodilatation in rat mesenteric artery via inhibiting voltage-dependent calcium channel-mediated extracellular Ca(2+) influx and receptor-mediated Ca(2+) influx and release.
Acetophenones ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Calcium ; metabolism ; Calcium Chloride ; pharmacology ; Endothelium, Vascular ; drug effects ; physiology ; Extracellular Space ; drug effects ; metabolism ; Female ; In Vitro Techniques ; Intracellular Space ; drug effects ; metabolism ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Norepinephrine ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Chloride ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Serotonin ; pharmacology ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects
7.Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.
Dong Jun SUNG ; Hyun Ju NOH ; Jae Gon KIM ; Sang Woong PARK ; Bokyung KIM ; Hana CHO ; Young Min BAE
Experimental & Molecular Medicine 2013;45(12):e67-
Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K+ (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca2+-activated K+, inward rectifier K+ and ATP-sensitive K+ channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca2+ channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, alpha-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.
4-Aminopyridine/pharmacology
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Action Potentials
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Animals
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Calcium Channel Blockers/pharmacology
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Calcium Channels/metabolism
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Cells, Cultured
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Ketanserin/pharmacology
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Male
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Mesenteric Arteries/drug effects/*metabolism/physiology
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Muscle Contraction
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Muscle, Smooth, Vascular/cytology/drug effects/metabolism/physiology
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Myocytes, Smooth Muscle/drug effects/metabolism/physiology
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Nifedipine/pharmacology
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Potassium Channel Blockers/pharmacology
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Potassium Channels, Voltage-Gated/antagonists & inhibitors/*metabolism
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Protein Kinase Inhibitors/pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptor, Serotonin, 5-HT2A/*metabolism
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Serotonin/*pharmacology
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Serotonin 5-HT2 Receptor Antagonists/pharmacology
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Spiperone/pharmacology
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*Vasoconstriction
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src-Family Kinases/antagonists & inhibitors/*metabolism