• The Korean Journal of Physiology
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• v.24 no.1
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• pp.91-102
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• 1990

The effects of extracellular $Ca^{2+}$ and various $Ca^{2+}$ antagonists on endothelium-dependent relaxation to acetylcholine were studied in the isolated rabbit thoracic aorta in order to elucidate the control mechanism of endothelium derived relaxing factor (EDRF) release. Endothelium was removed from aortic strips by gentle rubbing with cotton ball. The effect of hemoglobin on basal tension was also observed with hemolysate. The results obtained were as follows: 1) Endothelium-dependent relaxation (EDR) to acetylcholine (ACh) showed biphasic pattern; the initial rapid relaxation phase and the late slow relaxation phase. 2) With the depletion of the extracellular $Ca^{2+}$, EDR was gradually suppressed, especially the late slow relaxation. 3) Verapamil, nifedipine, $Mn^{2+}$ and $Cd^{2+}$ had not any effect on EDR, while $La^{3+}$ and $Co^{2+}$ suppressed EDR completely. 4) The resting tension of the strips with rubbed endothelium was not altered by the addition of hemoglobin. That of the strips with intact endothelium, however, was enhanced and EDR to ACh was completely blocked From these results, we suggest that extracellular $Ca^{2+}$ is necessary for ACh-induced slow relaxation while $Ca^{2+}$ antagonists have not any effect on EDR.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.67-71
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• 2002

This study investigated the relaxation effects of Crataegi Fructus(CF, Crataegus pinnatifida Bunge) on the contraction evoked by phenylephrine in rabbit carotid artery, and also analyzes antioxidative status in vitro. CF revealed siginificant relaxation on phenylephrine-induced arterial contraction. It's relaxant effect statistically significant in both in the presence of endothelium and absence of endothelium, but statistically exerted more strong relaxation in the presence of endothelium. CF increased in vitro nitric oxide(NO) production in dose-dependent manner. Also, they reduced malondiaidehyde(MDA) concentrations, phosphatidyl choline-liposome(PCOOH) contents, linoleic acid-induced lipid peroxidation and exerted 1,1-diphenyl-2- picryl-hydrazyl(DPPH) radical scavenging effect, in vitro. These results indicate that Crataegi Fructus would be effective in relaxing arterial contraction and it's antioxidative effects may be involved in endothelium-dependent relaxation of artery via vascular protective properites.

• BMB Reports
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• v.41 no.3
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• pp.223-229
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• 2008

Reactive oxygen species (ROS) are implicated in vascular homeostasis. This study investigated whether ${O_2}^{\cdot^-}$, the foundation molecule of all ROS, regulates vasomotor function. Hence, vascular reactivity was measured using rat thoracic aortas exposed to an ${O_2}^{\cdot^-}$ generator (pyrogallol) which dose-dependently regulated both $\alpha$-adrenergic agonist-mediated contractility to phenylephrine and endothelium-dependent relaxations to acetylcholine. Pyrogallol improved and attenuated responses to acetylcholine at its lower (10 nM - 1 ${\mu}M$) and higher (10 - 100 ${\mu}M$) concentrations, respectively while producing the inverse effects with phenylephrine. The endothelial inactivation by L-NAME abolished acetylcholine-induced vasodilatations but increased phenylephrine and KCl-induced vasoconstrictions regardless of the pyrogallol dose used. Relaxant responses to sodium nitroprusside, a nitric oxide donor, were not affected by pyrogallol. Other ROS i.e. peroxynitrite and $H_2O_2$ that may be produced during experiments did not alter vascular functions. These findings suggest that the nature of ${O_2}^{\cdot^-}$-evoked vascular function is determined by its local concentration and the presence of a functional endothelium.

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.82-86
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• 2003

Objective : To examine the inhibition of 5-Hydroxytryptamine(5-HT) induced vasocontraction of the water extract of Acanthopanax senticosus Harms roots (ASR) on rat thoracic Aorta and mesenteric artery with and without endothelium. Methods : Segments of thoracic aorta and mesenteric artery obtained from rats immediately after delivery were mounted in organ baths superfused on a polygraph. Results : We found that the thoracic aorta segments responded to the water extract of ASR with a dose-dependent and concentration-dependent vasorelaxation. 5-HT produced a concentration-dependent contraction of the thoracic aorta and mesenteric artery. At high concentrations of ASR, the inhibition responses were 93.7% (Jang-su), 93.5% (Heok-ryong-kang-sung), 92.8% (Mt. Back-doo), and 83.5% (Yeon-byun) of the maximum 5-HT induced contraction. At high concentrations of ASR, the relaxational response at thoracic aorta and mesenteric artery wi1h endothelium were 95.2% and 94.6%; without endothelium were 93.5% and 92.5% of 1he maximum 5-HT induced contraction. Conclusions : In conclusion, the effect of water extract of ASR had potent inhibition at 5-HT and the effect of ASR in isolated thoracic aorta and mesenteric artery showed dose-dependent inhibition but endothelium-independent response.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.125-132
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• 1997

Our previous study showed that in vivo treatment of spontaneously hypertensive rats (SHR) with protopanaxatriol ginsenosides (PPT) reduces the blood pressure and inhibits the con- tractions induced by endothelium-derived contracting factor (prostaglandin endoperoxide ($PGH_2$) and superoxide anion) in aorta isolated from SHR. The aim of the present study is to examine whether PPT improves endothelial functions in the isolated thoracic aorta of SHR in vitro. Treatments of aortic rings with PPT, purified ginsenoside $Rg_1$ ($Rg_1$) or indomethacin normalized endotheliuln-dependent relaxation to acetylcholine, but not with protopanaxadiol ginsenosides (PPD) and purified ginsenoside Rb1 (Rb1). The effects of PPT were dose-dependent. PGH,- and oxygen free radical-inducted contractions in rat aorta without endothelium were inhibited by PPT or $Rg_1$, but not by PPD or $Rb_1$. Contractions induced by PGF2$\alpha$, U-46619, a stable thromboxane A2 agonist or KCI (60 mM) were not inhibited by PPT, $Rg_1$ or $Rb_1$. These findings demonstrate that PPT but not PPD scavenges the oxygen-derived free radicals and/or antagonize the effects of $PGH_2$ in the vascular smooth muscle and may explain the hypotensive effect of ginseng in the SHR.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.389-396
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• 2009

The ethanol extract of Persicaria perfoliata (EPP) induced relaxation of the phenylephrine-precontracted aorta in a dose-dependent manner, which was abolished by removal of functional endothelium. Pretreatment of the aortic tissues with NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4}-oxadiazole-[4,3-${\alpha}$)-quinixalin-1-one (ODQ) inhibited the relaxation induced by EPP. However, EPP-induced relaxation was not blocked by pretreatment with indomethacine, glibenclamide, tetraethylammonium (TEA), atropine, or propranolol. Incubation of endothelium-intact thoracic aortic ring with EPP increased the production of cGMP, which was also blocked by pretreatment with L-NAME or ODQ. These results suggest that EPP dilates vascular smooth muscle via endothelium-dependent NO/cGMP signaling.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.727-734
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• 1994

To elucidate the effect of calcitonin gene-related peptide(CGRP), vasoactive intestinal peptide(VIP) and substance P was investigated with perivascular nerve stimulation and treatment of peptides from polygraph in the isolated renal artery of rabbit. 1. The neurogenic contraction induced by perivascular nerve stimulation was the frequency-dependent manner(264 Hz) in the isolated renal artery of rabbit. 2. CGRP and VIP caused the relaxation on the precontraction with noradrenaline($10{\mu}m$) on the presence and absence of endothelium in the isolated renal artery of rabbit. 3. Substance P caused the endothelium-dependent relaxation on the precontraction with noradrenaline($10{\mu}m$) in the isolated renal artery of rabbit. 4. CGRP and VIP inhibited the neurogenic contraction by the perivascular nerve stimulation(0.3 ms, 80 V, 50 Hz, 1 sec) on the absence and presence of endothelium in the isolated renal artery of rabbit. 5. Substance P inhibited on the neurogenic contraction by the perivascular nerve stimulation with the endothelium-dependent in the isolated renal artery of rabbit.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.90-90
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• 1995

The Influence of age on the endothelial modulation of angiotensin II (AII)-induced contractile response was investigated in isolated aortic rings of rats ranging in age from 0.7 to 20 months. Hemoglobin and L-NAME were used to examine whether age-related changes in the EDRF-releasing system were involved in endothelial modulation of All-induced contraction in rat aorta. In all five age groups (0.7, 1.5, 3, 6, 20 months), hemoglobin (10 ${\mu}$M) significantly enhanced All-induced contractile response only in aorta with endothelium intact. L-NAME (10 ${\mu}$M) Produced a significant enhancement in All responses in endothelium-intact aortas from rats aged 0.7 and 1.5 months, but it had no effect in aortas from older rats aged 6 and 20 months. Indomethacin (10 ${\mu}$M) did not affect All-induced contractile responses in both endothelium intact and removed aortas from rats at the age of 0.7 to 20 months. Hemoglobin (10 ${\mu}$M) abolished acetylcholine-induced relaxation response in aortas from young and old rats. L-NAME completely abolished the relaxation in aortas from young (0.7 and 1.5 months), but incompletely in aortas from older (6 and 20 months) rats. The sensitivity of endothelium-dependent relaxation to A23187 increased with age between ages of 0.7 and 6 months, with no further increase noted up to 20 months of age. These results suggest that endothelial modulation of AII-induced contraction in rat aorta might involve age-related alteration in EDRF-releasing system, probably via post-receptor mechanism.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.182-189
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• 1998

Administration of ginsenosides, a mixture of saponin extracted from Panax ginseng, decreased blood pressure in rat. Previous studies have shown that ginsenosides caused endothelium-dependent relaxation, which was associated with the formation of cyclic GMP, suggested that ginsenosides caused release of nitric oxide (NO) from the vascular endothelium. The aim of the present study was to characterize the endothelium-independent relaxation to ginsenosides in the isolated rat aorta. Ginsenosides caused a concentration-dependent relaxation of rat aortic rings without endothelium constricted with 25 mM KCI but affected only minimally those constricted with 60 mM KCI. Ginsenoside Rg3 (Rg3) was a more potent vasorelaxing agonist than total ginsenoside mixture and also the ginsenoside PPT and PPD groups. Relaxation to ginsenosides were markedly reduced by TEA, but not by glibenclamide. Rg3 significantly inhibited Cal'-induced concentration-contraction curves and the "50a2'influx in aortic rings incubated in 25 mM KCI whereas those responses were not affected in 60 mM KCI. Rg3 caused efflux of $"Rb in aortic rings that was inhibited by tetraethy- lammonium (TEA), an inhibitor of Ca"-dependent K'channels, but not by glibenclamide, an inhibitor of AfP-dependent K'channels. These findings indicate that ginsenosides may induce vasorelaxation via activation of Ca2'-dependent K'channels resulting in hyperpolarization of the vas- cular smooth muscle with subsequent inhibition of the opening of voltage-dependent Caf'channels. These effects could contribute to explain the red ginseng-associated vasodilation and the beneficial effect on the cardiovascular system.

• Archives of Pharmacal Research
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• v.29 no.1
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• pp.1-15
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• 2006

Vascular endothelial cell injury or dysfunction has been implicated in the onset and' progression of cardiovascular diseases including atherosclerosis. A number of previous studies have demonstrated that the pro-oxidative and pro-inflammatory pathways within vascular endothelium play an important role in the initiation and progression of atherosclerosis, Recent evidence has provided compelling evidence to indicate that interleukin-4 (IL-4) can induce proc inflammatory environment via oxidative stress-mediated up-regulation of inflammatory mediators such as cytokine, chemokine, and adhesion molecules in vascular endothelial cells. In addition, apoptotic cell death within vascular endothelium has been hypothesized to be involved in the development of atherosclerosis. Emerging evidence has demonstrated that IL-4 can induce apoptosis of human vascular endothelial cells through the caspase-3-dependent pathway, suggesting that IL-4 can increase endothelial cell turnover by accelerated apoptosis, the event which may cause the dysfunction of the vascular endothelium. These studies will have a high probability of revealing new directions that lead to the development of clinical strategies toward the prevention and/or treatment for individuals with inflammatory vascular diseases including atherosclerosis.