• 대한수의학회지
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• 제45권4호
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• pp.507-515
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• 2005

Melatonin, the principal hormone of the vertebral pineal gland, participates in the regulation of cardiovascular system in vitro and in vivo. However, the effects of melatonin on vascular tissues are still vague. The aim of this study was to assess the relationship between phospholipase C (PLC) and nitric oxide synthase (NOS)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling cascade in the relaxatory action of melatonin in isolated rat aorta. Melatonin induced a concentration-dependent relaxation in phenylephrine (PE)- and KCl-precontracted endothelium intact (+E) aortic rings. In KCl-precontracted +E aortic rings, the melatonin-induced vasorelaxation was not inhibited by endothelium removal or by pretreatment with NOS inhibitors, L-$N^G$-nitor-arginine (L-NNA) and L-$N^G$-nitor-arginine methyl ester (L-NAME), guanylate cyclase (GC) inhibitors, methylene blue (MB) and 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). In PE-precontracted +E aortic rings, the melatonin-induced vasorelaxation was inhibited by endothelium removal or by pretreatment with L-NNA, L-NAME, MB, ODQ and 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC). Moreover, in without endothelium (-E) aortic rings and in the presence of L-NNA, L-NAME, MB and ODQ in +E aortic rings, the melatonin-induced residual relaxations and residual contractile responses to PE were not affected by NCDC, a PLC inhibitor. It is concluded that melatonin can evoke vasorelaxation due to inhibition of PLC pathway through the protein kinase G activation of endothelial NOS/cGMP signaling cascade.

• Journal of Chest Surgery
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• 제31권2호
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• pp.102-107
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• 1998

L-Arginine이 산화질소 생성의 전구물질로서 공헌하는 것 이외에 다른 기전에 의하여도 혈관이완을 일으키는가 구명하기 위하여 적출 흰쥐 흉부대동맥 표본에서 L-arginine에 의한 장력, 조직 산화질소 및 cGMP 함량 변동 등을 조사하여 다음과 같은 결과를 얻었다. 1. Phenylephrine(3.5$\times$10－6 mol/L) 수축 대동맥 표본은 L-arginine(10－9~10－3 mol/L)에 의해 용량의존 이완되었다. NG-Nitro-L-arginine methyl ester(L-NAME, 10－5 mol/L) 전처치에 의해 저농도 L-arginine(10－9~10－6 mol/L)에 혈관이완 효과는 소실되었으나 고농도 L-arginine(10－4~10－3 mol/L)의 이완효과는 도리어 증강되었다. 내피층 파괴 혈관 표본은 L-arginine에 대해 이완반응을 보이지 않았다. 2. L-NAME(10－5 mol/L) 존재하에 일어나는 L-arginine 이완효과는 indomethacin 전처치에 의해 영향받지 않으나, ouabain 전처치에 의해 유의하게 감약되었다. 또한 L-arginine 이완효과는 methylene blue에 의해 부분적으로 길항되었다. KCl(3.5$\times$10－2 mol/L) 수축 대동맥 표본은 L-arginine(10－9~10－3 mol/L)에 의해 L-NAME (10－5 mol/L) 처치와 무관하게 이완반응을 보이지 않았다. 3. L-NAME는 혈관조직 산화질소 함량을 감소시키며 이 감소효과는 L-arginine(10－4 mol/L)에 의해 영향받지 않았다. 또한 L-NAME는 혈관조직 cGMP 함량을 감소시키나 이 감소효과는 L-arginine에 의해 영향받지 않았다. 이상의 실험성적은 L-arginine이 내피세포의 산화질소 및 cGMP 생성과 무관한 기전을 통해서도 내피의존 혈관이완효과를 나타냄을 시사하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.315-324
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• 2016

Human cardiac fibroblasts (HCFs) have various voltage-dependent $K^+$ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide ($H_2O_2$) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether $H_2O_2$ could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of $H_2O_2$ stimulated $Ca^{2+}-activated$ $K^+$ ($K_{Ca}$) currents but not delayed rectifier $K^+$ or transient outward $K^+$ currents, all of which are VDKCs. $H_2O_2-stimulated$ $K_{Ca}$ currents were blocked by iberiotoxin (IbTX, a large conductance $K_{Ca}$ blocker). The $H_2O_2-stimulating$ effect on large-conductance $K_{Ca}$ ($BK_{Ca}$) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated $BK_{Ca}$ currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the $H_2O_2-stimulating$ effect on $BK_{Ca}$ currents. Using RT-PCR and western blot analysis, three subtypes of $K_{Ca}$ channels were detected in HCFs: $BK_{Ca}$ channels, small-conductance $K_{Ca}$ ($SK_{Ca}$) channels, and intermediate-conductance $K_{Ca}$ ($IK_{Ca}$) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to $H_2O_2$, but IbTX decreased $H_2O_2$-induced apoptosis. These data suggest that among the VDKCs of HCFs, $H_2O_2$ only enhances $BK_{Ca}$ currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through $BK_{Ca}$ channels.

• 대한한의학회지
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• 제31권6호
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• pp.47-57
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• 2010

Objective: The present study investigated the effect of ethanol extract of Cynanchum wilfordii (ECW) on vascular relaxation and vascular inflammation in rat artery isolated from rats and anti-inflammatory activity in human aortic smooth muscle cells (HASMC). Methods: Vascular tone and guanosine 3',5'-cyclic monophosphate (cGMP) production were examined in rat artery isolated from Sprague Dawley rats, in the presence of ECW. HASMC were incubated with tumor necrosis factor-alpha (TNF-${\alpha}$) or Angiotensin II for 24 h. Matrix metalloproteinase (MMP)-2 and anti-oxidant activity of ECW was investigated by pretreatment with ECW in HASMC. Results: Cumulative treatment of ECW relaxed aortic smooth muscles of rats in a dose-dependent manner. ECW-induced vasorelaxation was significantly decreased by pretreatment of L-arginine methyl ester (L-NAME) or oxadiazolo-quinoxalinone (ODQ). Furthermore, ECW treatment of thoracic aorta significantly increased cGMP production. Incubation of ECW with ODQ or L-NAME markedly decreased ECW-induced cGMP production. ECW treatment dose-dependently suppressed TNF-${\alpha}$- or Angiotensin II-induced increase in matrix metalloproteinase-2 expression in HASMC. Also, ECW exhibited 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity in vitro and reduced TNF-${\alpha}$-induced increase in reactive oxygen species production in a dose-dependent manner. Conclusions: Taken together, the results suggest that ECW exerts vascular relaxation via NO/cGMP signaling pathway and decreases MMP-2 expression via anti-oxidant activity.