• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.3
• /
• pp.149-155
• /
• 2003

The aim of the present study was to examine the effects of platycodin D and $D_3$, which are active components derived from the roots of Platycodon grandiflorum A. DC., on the contractile force of the i3olated rat aorta and blood pressure of the anesthetized rat, and also to elucidate its mechanism of action. Both phenylephrine (an adrenergic ${\alpha}1$-receptor agonist) and high potassium (a membranedepolarizing agent) caused great contractile responses in the isolated aortic strips. Platycodin D at high concentration $(24{\mu}g/ml)$ inhibited contractile responses induced by phenylephrine $(10^{-5}\;M)$ and high potassium $(5.6{\times}10^{-2}\;M)$, while low concentrations of platycodin D $(4{\sim}8{\mu}g/ml$) did not affect those responses. However, platycodin $D_3\;(8{\sim}32{\mu}g/ml)$ did not alter the contractile responses evoked by phenylephrine and high $K^+$. Interestingly, the infusion of platycodin $D_3$ (1.0 mg/kg/30 min) significantly reduced the pressor responses induced by intravenous norepinephrine. However, platycodin $D_3$ (1.0 mg/kg/30 min) did not affect them. Taken together, these results show that intravenously administered platycodin D depresses norepinephrine-induced pressor responses in the anesthetized rat, at least partly through the blockade of adrenergic ${\alpha}1$-receptors. Platycodin D also caused vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic ${\alpha}1$-receptors, in addition to an unknown direct mechanism. However, platycodin $D_3$ did not affect both norepinephrine-induced pressor responses and the isolated rat aortic contractile responses evoked by phenylephrine and high potassium. Based on these results, there seems to be much difference in the mode of action between platycodin D and platycodin $D_3$.

• Journal of Chest Surgery
• /
• v.40 no.4 s.273
• /
• pp.264-272
• /
• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• Journal of Chest Surgery
• /
• v.34 no.3
• /
• pp.203-211
• /
• 2001

배경: AT$_1$수용체의 길항제가 세포 수준에서 심근을 재관류 손사으로부터 보호할수 있다는 것으로 알려져 있지만, 생체내에서의 효과나 그 기전은 아직 명확히 밝혀지지 않았다. 본 연구에서는 백서 심근 허혈 모델을 이용하여, AT$_1$ 수용체의 길항제들 중 하나인 irbesartan이 심근이 재관휴 손상에 미치는 효과를 알아보고, 재관류 손상을 매개하는 한 각지 기전으로서 세포자멸의 기여에 대하여 연구하고자 하였다. 대상 및 방법: Sprague-Dawley 백서에서 무작용 부형약(10% gum arabic: 1군, 개체수=14관) irbesartan(50mg/kg/day :II 군, 개체수=12)을 각각 3일 동안 24시간마다 경구로 투여하였다. 실험동물의 좌 관상 동맥을 45분간 결찰하였다가, 그 후 2시간 동안 재관류시킨 다음 심장을 적출 하였다. TTC(triphenyltetrazolium chloride) 염색법을 이용하여, 허혈 노출 부위에 대한 심근 경색 부위의 비율을 측정하였다. Agarose gel 전기영동상의 DNa 분절 양상과 TUNEL(TdT-mediated dUCP nick end labeling) 염색을 관찰하여 세포자멸이 일어난 정도를 평가하였다. 세포자멸을 조절하는데 관여하는 것으로 알려진 Bcl-2(B-cell lymphoma 2 gene), Bad 등의 단백과 ERK (extracellular signal-regulated kinase), p-38 등 신호전달체계에 작용하는 MAPKs(mitogen-activated protein kinases)의 발현을 측정하기 위하여 Western blot을 시행하였다. 결과: 허혈 노출부위에 대한 심근 경색부위의 비율은 II군(42$\pm$2.7%)이 I군( 64.1$\pm$4.65)에 비해 유의하게 작았다.(p< 0.05), Agarose gel 전기영동상의 DNA laddering 양상은 I군에서 보다 높게 발현되었다. Bad와 ERK2의 발현은 두 군간에 유의한 차이가 없었다. 결론: AT$_1$수용체 길항제인 irbesartan은 생체에서 심근의 재관류 손상을 줄이는 효과가 있었다. 이 효과는 적어도 부분적으로 나만 심근세포의 세포자멸이 감소한 것에 기인한 것으로 설명할 수 있으며, 이 항-세포 자멸 효과는 Bcl-2의 발현증가와 관련이 있는 것으로 추정되었다.

• The Korean Journal of Nuclear Medicine
• /
• v.31 no.1
• /
• pp.9-18
• /
• 1997

The therapeutic efficacy of antipsychotic drugs is generally attributed to their ability to block dopamine $D_2$ receptors. Classical $D_2$ antagonists are not effective to treat negative symptoms and produce extrapyramidal side effects On the other hand, atypical antipsychotic agents ameliorate negative symptoms without producing extra-pyramidal side effects, and it is reported to be associated with blockade of serotonin $5-HT_2$ receptors. The purpose of this study was to evaluate the effect of risperidone on neuroreceptors in the rat brain by Quantitative autoradiography method. In acute treatment group, risperidone was injected into Peritoneal cavity of male Wistar rats with dose of 0, 0.1, 0.25, 0.5, 1.0 and 2.0mg/kg in each group(5/group), and they were decapitated after 2 hours. In chronic treatment group, risperidone was injected with dose of 0, 0.1, and 1mg/kg(I.P.) for 21 days and decapitated after 24 hours following last treatment. The effect of risperodone on the binding of [$^3H$]spiperone to $5-HT_2$ and $D_2$ receptors were analysed in 4 discrete regions of the striatum, nucleus accumbens, and frontal cortex by quantitative autoradiography Acute treatment with risperidone reduced cortical $5-HT_2$ specific [$^3H$]spiperone binding to 32% of vehicle-treated control. Subcortical $5-HT_2$ specific [$^3H$]spiperone binding was not affected at all dose groups whereas a significant reduction (57%) in $D_2$ specific [$^3H$]spiperone binding was observed in risperidone treated group at doses of 1-2mg/kg. Chronic treatment with risperidone produced a decrease in the maximal number of cortical $5-HT_2$ receptors to 51% and 46% of control in 0.1mg/kg & 1mg/kg treated group respectively. In conclusion, risperidone is a cortical serotonin receptor antagonist with relatively weak antagonistic action on dopamine receptors. These effects oil neuroreceptors may explain the therapeutic effect of risperidone as a atypical antipsychotic agents.