• Childhood Kidney Diseases
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• 제2권1호
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• pp.20-25
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• 1998

목적 : Endothelin-1은 cyclosporine A와 관련된 신독성의 발생에 관련될 것으로 생각되고 있다. 이에 저자 등은 cyclosporine A가 혈액 및 요중 endothelin-1치에 미치는 영향을 알아보고자 하였다. 방법 : 1996년 2월부터 1997년 3월까지 스테로이드 의존성 미세변화형 신증으로 진단받고 cyclosporine A를 투여받은 15세 미만의 환아 9례를 대상으로 cyclosporine A 투여 전과 투여 3개월 후의 혈장과 소변에서 endothelin-1치를 측정하였다. 평균 연령은 $8.3{\pm}4.6$세였다. 결과 : (1) 혈중 endothelin-1치는 cyclosporine A 투여 전에 $3.22{\pm}0.39$ pg/mL였고, cyclosporine A 투여 3개월 후에 $3.84{\pm}1.52$ pg/mL로 유의한 차이가 없었다(P=0.64). (2) 요중 endothelin-1치는 cyclosporine A 투여 전에 $21.8{\pm}5.8$ pg/mL였고 cyclosporine A 투여 3개월 후에 $20.3{\pm}3.1$ pg/mL로 유의한 차이가 없었다(P=0.30). 결론 : 혈액 및 요중 endothelin-1치는 비교적 단기간의 cyclosporine A 투여에 의해서는 유의한 변화를 보이지 않았으며, 향후 장기간의 cyclosporine A 투여가 endothelin-1치에 미치는 영향에 대한 연구도 필요할 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.763-770
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• 1998

A number of substances involved in the proliferation and differentiation of the tracheobronchial epithelium have been identified. The defects in the control of the proliferation and differentiation of tracheobronchial epithelial cells appear to constitute crucial steps in the transition of normal cells to neoplastic ones. Endothelin-1 is produced by tracheal epithelial cells, and its receptors are present in tracheal epithelial cells. However, the effect of endothelin-1 on the proliferation and differentiation of tracheal epithelial cells has not been clearly elucidated. This study was undertaken to investigate these actions of endothelin-1 in primary cultured cells of rat tracheal epithelia. Endothelin-1 stimulated proliferation of tracheal epithelial cells 1.5-fold when compared with that of control cells. Endothelin-1 increased mitogen-activated protein kinase (MAPK) activity. Herbimycin A, a tyrosine kinase inhibitor, inhibited endothelin-1-induced proliferation of epithelial cells. The treatment of endothelin-1 during the primary culture of tracheal epithelial cells increased AB-PAS-stained cell population and ciliated cell population 6.5 fold and 1.5 fold, respectively, when compared with those in control cells. The responsiveness to carbachol and forskolin in the $Cl^-$ secretion was increased 1.7 and 1.9 fold, respectively, in the endothelin-treated epithelial cells. These results indicated that endothelin-1 increases proliferation via MAPK pathway and stimulates differentiation to secretory and ciliated cells in rat tracheal epithelial cells.

• 약학회지
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• 제44권2호
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• pp.162-168
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• 2000

To investigate the effects of protein kinases on endothelin-1-induced phospholipase C activation and $Ca^{2+}$ mobilization in Rat-2 fibroblast, we measured the formation of inositol phosphates and intracellular $Ca^{2+}$ concentration with [$^3$H]inositol and Fura-2/AM, respectively. Endothelin-1 dose-dependently activated phospholipase C and increased intracellular $Ca^{2+}$ concentration. Protein kinase C activator PMA, significantly inhibited both phospholipase C activity and $Ca^{2+}$ mobilization induced by endothelin-1. Tyrosine kinase inhibitor, genistein, inhibited both. On the other hand, cyclic nucleotide (cAMP and cGMP) did not have any influence on the signaling pathway of phospholipase C-Ca$^{2+}$ mobilization induced by endothelin-1. These results suggest that protein kinase C and tyrosine kinase counteract on the signaling pathway of phospholipase C-Ca$^{2+}$ mobilization induced by endothelin-1 in Rat-2 fibroblast. fibroblast.

• Clinical and Experimental Pediatrics
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• 제50권12호
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• pp.1194-1199
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• 2007

목 적 : 본 연구자들은 전자간증, 부당 경량아, 자궁 내 발육지연 등의 질환들이 공통적으로 혈관내피세포의 기능 변화와 어느 정도 관련되어 있을 것으로 추론하였다. 따라서 전자간증 산모의 신생아, 부당 경량아의 제대혈관내피세포를 배양하여 제대의 혈관내피세포에서 발현되는 대표적인 혈관 수축작용 물질인 endothelin-1의 양을 측정한 후 정상 신생아 제대혈관 내피세포의 결과와 비교하여 각 질환에서 태아의 혈관내피세포의 endothelin-1 발현 기능에 어떤 차이가 있는지를 확인하고, 또한 배양된 정상아 제대혈관내피세포에 전자간증 산모의 신생아와 부당 경량아 및 정상아의 제대혈 혈청을 투여하여 발현된 endothelin-1의 양을 비교하여 혈청 내에 endothelin-1의 발현을 촉진시키는 인자가 있는지를 알아보았다. 방 법 : 전자간증으로 진단 받은 산모의 신생아를 전자간증군(n=7), 부당 경량아로 진단받은 신생아를 부당 경량아군(n=8), 정상 신생아를 정상군(n=12)으로 나누었다. 각 그룹에서 태어난 신생아 제대와 제대혈을 모아 제대혈은 그 혈청을 영하 $70^{\circ}C$ 이하에 보관하였다. 전자간증군, 부당 경량아군 및 정상군 신생아의 제대 혈관내피세포를 분리하고 배양하였다. 배양된 각각의 제대 혈관내피세포의 상층액에서 endothelin-1 level을 측정하였다. 다음에는 전자간증군, SGA군 및 정상군의 제대혈 혈장과 정상 신생아 제대 혈관내피세포를 함께 부양하여 그 상층액에서 endothelin-1 level을 측정하였다. 결 과 : 전자간증군, 부당 경량아군 및 정상군의 제대혈관내피세포를 배양하여 발현된 endothelin-1의 양을 측정한 결과 전자간증군과 SGA군의 제대혈관내피세포의 endothelin-1 발현은 정상군과 유의한 차이가 없었다. 그러나 배양된 정상아 제대혈관내피세포에 전자간증군과 SGA군의 제대혈 혈청을 투여하여 발현된 endothelin-1의 양은 정상군에 비하여 유의하게 증가되었다. 결 론 : 전자간증 신생아나 부당 경량아의 혈관내피세포의 기능이상을 유발하는 인자가 전자간증과 부당경량아 제대 혈청내에 존재할 가능성이 있을 것으로 생각된다.

• Journal of Chest Surgery
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• 제40권4호
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• pp.247-255
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• 2007

배경: 일반적으로 선천성 심장질환의 수술교정에는 체외 심폐 순환(체외순환)이 이용된다. 체외순환과 관련된 폐손상이 잘 알려져 있는데, 임상적으로 산소화의 저하, 폐유순도의 감소, 폐혈관의 저항과 반응성의 증가의 소견을 보이며 수술 후 합병증 및 사망의 중요한 원인이 된다. 이러한 폐손상의 원인은 보체의 할성화, 호중구의 축적, 산소라디칼손상을 포함하여 아주 다양하지만, 폐혈관 내피의 손상과 그에 의한 endothelin-1 발현의 변화가 주된 원인이라고 보고되고 있다. 저자들은 복막 투석이 혈장 endothelin-1의 제거에 기여할 수 있는지 여부에 대한 연구를 하였다. 대상 및 방법: 2005년 3월 부터 2006년 3월 사이에 18명의 환자를 대상으로 하였다. 혈장 검체는 수술 전후로 채취하였고, 수술 후 복막 투석 카테터를 삽입하여 체외순환 이탈 후의 복막 유출액 검체를 채취하였다. Endothelin-1의 농도측정은 ELISA (enzyme Linked Immunosorbent assay)로 시행하였다. 결과: 술 전에 측정된 endothelin-1 값이 술 전 폐혈류 혹은 폐동맥압의 증가의 진단을 가진 환아에서 유의하게 높았다 (4.2 vs 1.8 pg/mL, p<0.001). 수술 전 혈장 endothelin-1의 평균 농도는 $3.61{\pm}2.17pg/mL$이었고, 체외순환 이탈 직후는 $5.33{\pm}3.72 pg/mL$로 가장 높게 측정되었다. 복막 투석 시작 후, 농도는 감소하기 시작하여 체외순환 이탈 직후에 비해 18시간째에는 유의하게 낮은 농도를 나타내었다(p=0.036). 결론: 혈장 endothelin-1 농도가 체외순환 이탈 직후에 가장 높게 측정되었고, 복막 투석 후 감소하기 시작하는 소견은 복막 투석으로 혈장 endothelin-1이 제거될 수 있는 가능성을 강하게 시사한다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.193-193
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• 1996

Endothelin-1, which is a peptide originally isolated from cultured porcine aortic cell, has been found to play a crucial role in potentiating the vasoconstriction mitogenesis, and chemotaxis. In the present study, we examined the level of endothelin-1 in the brain, spinal cord and blood from rat with experimental allergic encephalomyelitis(EAE). At the peak stage of EAE(grade 3), endothelin-1 level in the spinal cord of rat with EAE increased two folds as compared with that of sham-treated rats, and subsequently decreased to the level of control at the recovery stage. In the endothelin-1 immunocytochemistry, endothelin-1 immunopositive cells and ED-1, macrophage marker immunopositive cells observed in the spinal cord of peak stage(grade 3). These Findings suggest that endothelin-1 play the important role in progression of EAE.

• 대한물리치료과학회지
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• 제13권2호
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• pp.99-119
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• 2006

Endothelin (ET) is a 21 amino acid peptide with multifunctional effects on the vasculature as well as a variety of other cell types such as respiratory, gastrointestinal, urogenital, endocrine, central nervous systems, and others. Endothelin has emerged as a modulator by autocrine and paracrine actions for many cellular activities, including vasoconstriction, cell proliferation, hormone production, neurotransmitter and/or neuromodulator. The endothelin family consists of three closely related peptides, ET-1, ET-2, and ET-3 derived from separate genes, such as chromosome 6, 1, and 20, respectively. ET-1 is the predominant isoform produced in the cardiovascular system and about which most is known. Endothelin receptors are seven-transmembrane GTP-binding protein-coupled receptors, which are classified into endothelin-A (ETA) and endothelin-B (ETB) receptors. Interestingly, recent evidence is accumulating to suggest that ET -1 may contribute to a variety of pain states such as allodynia and hyperalgesia in animals and humans. Therefore, in this review the biological characteristics and contraction-related mechanism of endothelin-1 in mammalian cells will be summarized. Especially, we focus on multifunctional roles for ET-1 in noxious stimulation-induced pain for the study of pain specialized physical therapy.

• 대한물리치료과학회지
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• 제9권4호
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• pp.45-52
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• 2002

Rats that are fed a fructose-rich diet develop hypertension, insulin resistance, and hypertriglyceridemia. To elucidate whether altered expression levels of endothelin-1 and nitric oxide synthase are related to the development of insulin-resistant hypertension, we examined the present study. Male Sprague-Dawley rats were fed a fructose-rich diet for 5 weeks. Systolic blood pressure significantly increased in fructose-fed rats. While serum free fatty acid and plasma nitrite/nitrate levels did not significantly differ between the fructose-fed and control groups, plasma insulin and serum triglyceride concentrations significantly increased in the former. Endothelin-1 mRNA expression in the aorta increased in fructose-fed rats. Neither the protein expression of constitutive nitric oxide synthase nor that of inducible nitric oxide synthase were significantly affected by fructose feeding. However, nitrite/nitrate levels in the aorta were significantly increased. These results suggest that an increase in vascular endothelin-1 is an important contributing factor to the development of hypertension in fructose-fed rats. However, the vascular nitric oxide pathway may not be causally related to the development of fructose-induced hypertension.

• The Korean Journal of Pain
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• 제11권1호
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• pp.36-40
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• 1998

Background: Recently, it has been demonstrated that endothelin(ET) and endothelin related peptides are present in the blood and plasma ET levels are increased after operation. But the causes of increasing plasma ET levels are not clearly understood. This current study was to investigate the relationship between postoperative pain and endothelin. Methods: Thirty adult patients, scheduled for upper abdominal operation under general anesthesia, were included. After operation, epidural catheterization was done for postoperative analgesia. Before induction, on complained of pain and 1 hour after analgesics administration, blood samples were obtained to measure plasma ET levels. Plasma ET concentration was determined by radioimmunoassay. Pain score was measured by visual analogue score(VAS). Mean arterial pressure(MAP) and heart rate(HR) were also recorded every sampling time. Results: There were no significant changes in plasma ET levels at the time before induction versus at the time of the pain complaints and at 1 hour after analgesic administration. Pain score was significantly reduced after epidural analgesia. There was no significant correlations between pain score and plasma ET levels. There were no significant correlation between plasma ET levels and either MAP or HR. Conclusions: These results indicate that there is lack of relationship between postoperative pain and endothelin.

• Journal of Korean Neurosurgical Society
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• 제29권4호
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• pp.451-460
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• 2000

Objective : This experiment is aimed at clarifying the characteristics of spasmodic basilar arteries in the rabbits of subarachnoid hemorrhage(SAH) with observation of vascular response to nitric oxide(NO) and endothelin-1. Material and Methods : Seventy-nine New Zealand white rabbits were divided into 4 groups : control(n=17), sham operation(n=13), postictal-2-day(n=25), and postictal-7-day group(n=24). Rabbits in the postictal-2-day group and postictal-7-day group underwent transfemoral vertebral angiography 2 days and 7 days after SAH respectively. A vascular ring of spasmodic basilar artery was harvested and suspended in organ chamber($37^{\circ}C$) to observe isometric tension changes in response to NO and endothelin-1 under both high(95% $O_2$/5% $CO_2$) and low(95% $N_2$/5% $CO_2$) $O_2$ tension. To investigate the vascular response to NO, acetylcholine from $10^{-7}M$ to $3{\times}10^{-4}M$ concentration was applied to basilar artery ring precontracted with histamine $10^{-6}-10^{-5}M$ in the organ chamber. The vascular response to endothelin-1 was observed by applying endothelin-1 from $10^{-11}M$ to $3{\times}10^{-8}M$ concentration into organ chamber. Results : Seven of 15 live rabbits which underwent angiography 2 days after SAH, were confirmed to develop vasospasm($64.3{\pm}11.2%$) whereas seven of 13 live rabbits which underwent angiography 7 days after SAH, were confirmed to develop vasospasm($64.9{\pm}10.9%$). In all groups, hypoxia significantly reduced the vascular relaxation of basilar arteries to NO. However, hypoxia made no influence on the vascular contraction of basilar arteries to endothelin-1 in all groups. In vascular relaxation of basilar arteries to NO under high $O_2$ tension between groups, the maximum relaxation of basilar arteries in the postictal-7-day group was significantly reduced compared to the postictal-2-day group. In vascular contraction of basilar arteries to endothelin-1 under high $O_2$ tension between groups, the maximum contraction of basilar arteries in the postictal-7-day group was significantly reduced compared to the postictal-2-day group. Conclusions : This experiment suggests that the characteristics of vascular response to NO and endothelin-1 in the spasmodic basilar arteries of rabbits observed 2 days after SAH is different from those observed 7 days after SAH.