• Journal of Korean Neurosurgical Society
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• v.39 no.3
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• pp.215-220
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• 2006

Objective : Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet been reported whether L-type $Ca^{2+}$ channels playa role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study was undertaken to clarify the role of L-type $Ca^{2+}$ channels in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on L-type $Ca^{2+}$ channels currents in freshly isolated smooth muscle cells from rat basilar artery. Methods : The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Results : Patch clamp studies revealed a whole-cell current which resembles the L-type $Ca^{2+}$ current reported by others. The amplitude of this current was decreased by nimodipine and increased by Bay K 8644. Genistein[n=5], tyrphostin A-23[n=3]. A-25[n=6] $30{\mu}M$ reduced the amplitude of the L -type $Ca^{2+}$ channel current in whole cell mode. In contrast, diadzein $30{\mu}M$ [n=3]. inactive analogue of genistein, did not decrease the amplitude of the L-type $Ca^{2+}$ channels current. Conclusion : These results suggest that tyrosine kinase inhibitors such as genistein, tyrphostin A-23, A-25 may relax cerebral vessel through decreasing level of intracellular calcium, [$Ca^{2+}$]i, by inhibition of L-type $Ca^{2+}$ channel.

• Korean Journal of Pharmacognosy
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• v.16 no.2
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• pp.65-72
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• 1985

These studies were conducted to investigate the effect of 'Inchungbaek' water extract on analgesic and sedative actions, the relaxing action of isolated ileums, vasodilating action and blood pressure. The results of these studies were summarized as follows: Analgesic and sedative actions of 'Inchungbaek' were recognized in mice and rats. The relaxing action of isolated ileums were seen in mice and rabbits, antagonist action was seen acetylcholine and $BaCl_2-induced$ contraction of isolated ileums, and then recognized direct action in the ileum smooth muscle. Hypotensive and vasodilating actions due to vascular smooth muscle relaxation were noted in rabbits and cats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1629-1635
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• 2006

The migration of vascular smooth muscle cells (VSMC) and the production of matrix metallopreteinases-9 (MMP-9) may play a key role in the development of atherosclerosis. In this study, we have more extensively investigated the inhibitory effect of UR on MMP-9 activity and TNF-${\alpha}$ induced human aortic smooth muscle cells (HASMC) migration. The result from gelatin zymography showed that UR inhibited MMP-9 activity in a dose-dependent manner (IC50 = 55 g/ml). In addition, UR strongly inhibited the migration of HASMC induced by TNF-treatment (IC50 = 125 g/ml), although it has very low cytotoxic effect on HASMC (IC50 > 500 g/ml). These results suggest that UR is a potential anti-atherosclerotic agent through inhibition of MMP-9 activity and VSMC migration.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.142.1-142.1
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• 2001

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.437-445
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• 2018

${\alpha}$-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms, but the mechanism responsible for this activity has not been determined. To determine the role played by ICB on the regulation of vascular tone, we investigated the inhibitory effects of ICB on vascular contractile responses by adrenergic ${\alpha}$-receptor agonists. In addition, we investigated the role on myosin light chain (MLC) phosphorylation and cytosolic calcium concentration in vascular smooth muscle cells (VSMC). In aortic rings isolated from C57BL/6J mice, ICB significantly attenuated the contraction induced by phenylephrine (PE) and norepinephrine (NE), whereas ICB had no effects on KCl (60 mM)-induced contraction. In vasculatures precontracted with PE, ICB caused marked relaxation of aortic rings with or without endothelium, suggesting a direct effect on VSMC. In cultured rat VSMC, PE or NE increased MLC phosphorylation and increased cytosolic calcium levels. Both of these effects were significantly suppressed by ICB. In conclusion, our results showed that ICB regulated vascular tone by inhibiting MLC phosphorylation and calcium flux into VSMC, and suggest that ICB has anti-hypertensive properties and therapeutic potential for cardiovascular disorders related to vascular hypertension.

• The Korean Journal of Physiology
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• v.27 no.2
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• pp.199-207
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• 1993

To study the underlying mechanism through which the endothelium-dependent relaxation is inhibited by blocking the $Na^+\;-K^+$ pump, the effects of $Na^+\;-K^+$ pump blockade on the release of EDRF and its relaxing activity were examined, using organ bath study, bioassay technique, and cGMP measurement. Endothelium-dependent relaxation was attenuated by blocking the $Na^+\;-K^+$ pump in the vascular ring with intact endothelium. In bioassay experiment EDRF release was decreased with the blockade of the $Na^+\;-K^+$ pump in the EDRF donor strip. Endothelium-dependent increase of cGMP level was suppressed by inhibiting the $Na^+\;-K^+$ pump in the test strips. The magnitude of relaxation of test strip which was induced by the perfusate that had passed through the EDRF donor strip was decreased with the blockade of the $Na^+\;-K^+$ pump in the test strip. Therefore, it could be suggested that the attenuation of endothelium-dependent relaxation caused by inhibiting $Na^+\;-K^+$ pump activity is due to both the decreased release of EDRF from endothelial cells and the decreased sensitivity of the smooth muscle cells to EDRF.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.69-79
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• 2020

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H₂O₂) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.

• Journal of Food Hygiene and Safety
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• v.26 no.3
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• pp.187-191
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• 2011

Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell(VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of atherosclerosis. The aim of this study was to assess the effect of YP 12, a newly synthesized obovatol derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The anti-proliferative effects of YP 12 on rat aortic VSMCs were examined by direct cell counting and by using $[^3H]$ thymidine incorporation assays. It was found that YP 12 potently inhibited the growth of VSMCs. The pre-incubation of YP 12 (1-4 ${\mu}M$) significantly inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. In accordance with these findings, YP 12 revealed blocking of the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Whereas, YP 12 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. These results also show that YP 12 may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.

• Molecules and Cells
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• v.20 no.3
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• pp.429-434
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• 2005

Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity. In this study, we investigated its effects on lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC-induced DNA synthesis and cell proliferation in VSMCs, as well as migration of the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity and the lysoPC-induced increases in intracellular reactive oxygen species (ROS). These results indicate that the inhibitory effects of berberine on lysoPC-stimulated VSMC proliferation and migration are attributable to inhibition of ROS generation and hence of activation of the ERK1/2 pathway. This suggests that berberine has potential in the prevention of atherosclerosis and restenosis.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.351-356
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• 1999

The present study was aimed at investigating whether the calcium current in the vascular smooth muscle (VSM) cells is altered in renal hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in Sprague-Dawley rats. Rats without clipping the renal artery or implanting DOCA were used as control for 2K1C and DOCA-salt hypertension, respectively. Four weeks after clipping, systolic blood pressure was significantly higher in 2K1C rats than in control $(192{\pm}24\;and\;119{\pm}4$ mmHg, respectively, n=16 each). DOCA-salt rats also showed a higher blood pressure $(180{\pm}15$ mmHg, n=18) compared with control $(121{\pm}6$ mmHg, n=14). VSM cells were enzymatically and mechanically isolated from basilar arteries. Single relaxed VSM cells measured $5{\sim}10\;{\mu}m$ in width and $70{\sim}150\;{\mu}m$ in length were obtained. VSM cells could not be differentiated in size and shape between hypertensive and normotensive rats under light microscopy. High-threshold (L-type) calcium currents were recorded using whole-cell patch clamp technique. The amplitude of the current recorded from VSM cells was larger in 2K1C hypertension than in control. Neither the voltage-dependence of the calcium current nor the cell capacitance was significantly affected by 2K1C hypertension. By contrast, the amplitude of the calcium current was not altered in DOCA-salt hypertension. These results suggest that high-threshold calcium current of the VSM cells is altered in 2K1C hypertension, and that calcium channel may not be involved in calcium recruitment of VSM in DOCA-salt hypertension.