• Journal of Oral Medicine and Pain
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• v.21 no.1
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• pp.79-87
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• 1996

The purpose of this study was to assess the vascular changes after thermophysical therapies using ice pack and ultrasound, investgate the mechanism of peripheral vasodilation by sympathetic nerve, and to observe the effects of the ergotamine to the thermophysical therapy. The author had used 16 healthy rabbits which were divided into 2 groups : with and without administration of ergotamine. Experimental animals were sacrificed 5, 10, 20 minutes after experiment, and were examined with gross and stereoscope of resin casting blood vessel models. The results were as follows : 1. Vasodilation was not remarkably found in the group with administration of egrotamine after thermophysical therapy. 2. Vasodilation was remarkably found in the group without administration of ergotamine after thermophysical therapy. 3. Vasodilation was increased in the group without administration of ergotamine, but not remarkably found in the group with administration of ergotamine in lapse of time 4. Thermophysical therapy was most effective to arterioles. Our data suggest that the dilation of peripheral blood vessels from thermophysical therapy was controlled by sympathetic nerve, because the blood vessels did not changed after administration of ergotamines which was a sympathetic nerve blocker.

• The Korean Journal of Pain
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• v.29 no.4
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• pp.229-238
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• 2016

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

• Herbal Formula Science
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• v.11 no.2
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• pp.125-134
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• 2003

We have examined the relaxational response to the water extract of Angelica gigas $N_{AKAI}$ (AG), Gingko biloba $L_{INNE}$ (GB), Acanthopanax senticosus $H_{ARMS}.$ (AP) and Augumented-Four-Substance Decoction (AG-FSD, GB-FSD, AP-FSD) in isolated thoracic aorta from sprague dawley(SD) rat. Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to AG, GB, AP and AG-FSD, GB-FSD, AP-FSD were investigated in vessels precontracted with 5-hydroxytryptamine(5-HT) were compared in vasodilation effect. We found that the thoracic aorta segments responded to AG, GB, AP and AG-FSD, GB-FSD, AP-FSD with a dose-dependent vasodilation. The 5-hydroxytryptamine induced contraction at $10^{-4}M$ were inhibited by 26.3%, 75.8%, 87.5% and 6.9%, 22.6%, 30.8% after addition of the 0.1 g/mL water extract of AG, GB, AP and AG-FSD, GB-FSD, AP-FSD. In conclusion, AG, GB, AP and AG-FSD, GB-FSD, AP-FSD induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. AP-FSD has very potent vasodilation.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.229-238
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• 2014

Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.938-942
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• 2002

We have examined the relaxational response to the water extract of Rheum palmatum L.(ERP) and water extrc alcohol processed Rheum palmatum L.(ARP) in isolated thoracic aorta from sprague dawley (SD) rat. Rat thoracic aort investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to ERP and ARP investigated in vessels precontracted with 5-hydroxytryptamine(5-HT). We found that the thoracic aorta segments respo to ERP and ARP with a dose-dependent vasorelaxation. We found that ; The thoracic aorta segments responded to I and ARP with a dose-dependent vasodilation. The 5-HT induced contraction at 10/sup -4/M were inhibited by 71.7% and a: after addition of the 0.01 g/mL water extract of ERP and ARP. The 5-HT induced contraction at 10/sup -4/M were inhibite 100% after 10/sup -3/M emodin. The concentration of emodin was 0.027% and 0.098% in ERP and ARP. In condusion, ERP ARP induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. and it has pi vasodilation.

• Korean Journal of Clinical Pharmacy
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• v.21 no.1
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• pp.6-13
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• 2011

Bolus intravenous injection of adenosine resulted the temporal decrease of systemic blood pressure and heart rate in the anesthetized rats. Adenosine also resulted the persistent decrease of contractility and heart rate in the isolated spontaneously beating rat right atria. Both of the above inhibition effets of adenosine were increased by the pretreatment of NBI (nitrobenzylthioinosine), whitch is an adenosine transport inhibitor, but decreased by the pretreatment of 8- phenyltheophy1line, which is an adenosine antagonist. In isolated thoracic aorta ring segment of normotensive rats, intact rings were relaxed by adenosine ($42.3{\pm}8.7%$) and ATP ($85.9{\pm}15.8%$) in the concentration of $10^{-4}M$, but rubbed rings were relaxed by adenosine ($35.2{\pm}1.9%$) and ATP ($11.3{\pm}9.0%$) in $10^{-4}M$. After pretreatment of L-NAME (N-Nitro-Larginine methyl ester), which is an NO inhibitor, adenosine-induced relaxation was not affected, but ATP-induced relax ation was significantly inhibited (P<0.01). Meanwhile, adenosine resulted almost same as vasorelaxation in isolated thoracic aorta of SHR comparing to those of normotensive rats. But, vasodilation responses of ATP in intact rings of SHR are significantly inhibited comparing to those of normotensive rats. Adenosine-induced relaxation is attenuated after 8-phenyltheophylline pretreatment, but increased after NBI pretreatment. However, ATP-induced relaxations are not affected by 8-phenyltheophylline or NBI pretreatment. These results suggested that the hypotensive effects of adenosine was due to the decrease of contractile force and heart rate through the A1 receptor and vasodilation are mediated by A2 receptor of the vascular smooth muscle. And, the heart protective and vasodilation effects of adenosine might suggest that it would be useful in the acute treatment of coronary artery disease.

• Journal of Korean Neurosurgical Society
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• v.52 no.3
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• pp.172-178
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• 2012

Objective : The aim of this study was to determine the role of intra-arterial (IA) nimodipine injections for cerebral vasospasm secondary to ruptured subarachnoid hemorrhage (SAH) and to investigate the factors that influence vasodilation and clinical outcomes. Methods : We enrolled 29 patients who underwent aneurysm clipping for ruptured cerebral aneurysms between 2009 and 2011, and who received IA nimodipine after subsequently presenting with symptomatic vasospasm. The degree of vasodilation shown in angiography was measured, and the correlation between the degree of vasodilation and both the interval from SAH to cerebral vasospasm and the interval from clipping to cerebral vasospasm was determined. The change in blood flow rate after IA injection was assessed by transcranial Doppler ultrasound. Multiple clinical parameters were completed before and after IA nimodipine injection to evaluate any improvements in clinical symptoms. Results : For eight patients, Glasgow Coma Scale (GCS) scores increased by two or more points. The regression analysis demonstrated a positive correlation between the change in GCS scores after IA nimodipine injection and the change in blood vessel diameter (p=0.025). A positive correlation was also observed between the interval from SAH to vasospasm and the change in diameter (p=0.040); and the interval from clipping to vasospasm and the change in diameter (p=0.022). Conclusion : IA nimodipine injection for SAH-induced vasospasm led to significant vasodilation in angiography and improvement in clinical symptoms without significant complications. Our findings suggest that IA nimodipine injection should be utilized when intractable vasospasm develops despite rigorous conservative management.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.4
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• pp.287-298
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• 2020

Ca²⁺ signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca²⁺ signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca²⁺ concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K⁺ efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca²⁺ influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca²⁺-permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca²⁺-sensitive K⁺ channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca²⁺ signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca²⁺ dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.69-74
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• 2004

We have examined the relaxative response to the water extract of Rheum undulatum L. (ERU) and water extract of alcohol steamed Rheum undulatum L. (SRU) with isolated thoracic aorta from sprague dawley (SD) rat. Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to ERU and SRU were investigated in vessels precontracted with 5-hydroxytryptamine(5-HT). We found that the thoracic aorta segments responded to ERU and SRU with a dose-dependent vasorelaxation : The thoracic aorta segments responded to ERU and SRU with a dose-dependent vasodilation. The amounts of emodin were 0.063%, 0.076% and 0.145% in ERU and SRU, respectable. The 5-HT induced contraction at 10-4M were inhibited by 85.2±4.76% and 84.0±2.91% after addition of the 0.1mg/mL water extract of ERU and SRU. The 5-HT induced contraction at 10/sup -3/M were inhibited by 100% after 10/sup -3/M emodin. In conclusion, vasodilation effect of the water extract of Rheum undulatum L. in rat thoracic aorta was not decreased according to the processing of alcohol steamed Rheum undulatum L.

• Journal of Life Science
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• v.32 no.2
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• pp.175-188
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• 2022

Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IK_Ca channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI₂. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.