• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.191-191
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• 1996

BQ-123, a selective $ET_{A}$ receptor antagonist, reverses various responses induced by Endothelin-1 and it has been reported that BQ-123 ameliorates the cerebrovascular constriction, hypertension, and decrease of blood flow. Previously, we announced that the level of Endothelin-2 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of $ET_{A}$ receptor antagonist, BQ-123(10nmol) was done for visualizing the role of endothelin-1 on the pathogenesis of EAE. BQ-123 apparently blocked the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model following BQ-123, suggests that BQ-123 is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.192-192
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• 1996

Endothelin has $ET_{A}$ type and $ET_{B}$ type receptors, and it has been thought that ET-1 proves vasoconstriction effect via $ET_{A}$ receptor and vasodilation via $ET_{B}$ receptor. Recently, it has been reported that $ET_{B}$ receptor is also related to the vaso-constriction. Bosentan is a $ET_{A+B}$ receptor antagonist, and proves it's effect on trauma and ischemia. We already announced that the level of Endothelin-1 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of Bosentan, $ET_{A+B}$ receptor antagonist, (300nmol/body) was done for observing the role of endothelin-1 on the pathogenesis of EAE. Bosentan ameliorated the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model suggests that Bosentan is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.24 no.3
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• pp.134-145
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• 1998

Facial hyperpigmentation in women, which is considered to be a serious cosmetic disability and a cause of mental distress, requires proper management. Melanocyte dendricity is a crucial factor affecting epidermal pigmentation. We found that BQ-788, the endothelin-B (ETB) receptor antagonist, blocks the formation of multi-dendricity which is induced by cocultured keratinocytes. Melanocytes in vivo show numerous dendrites which are in close contact with multiple keratinocytes, forming the epidermal-melanin unit. While melanocytes transfer their melanosomes into the neighboring keratinocytes via dendrites, keratinocytes secrete many growth factors and cytokines that influence viability, morphology, and melanin formation of melanocytes. Endothelin-1 (ET-1), prostaglandin E2(PGE2), and leukotriene-C4 (LT-C4) have been suggested as the candidates for increasing dendricity. Other reports suggested that ET-1 has stimulatory effects on proliferation and melanin formation of melanocytes in vitro. In the present study, using type-specific ET receptor antagonists, we observed how the morphology of melanocytes could be modulated in a coculture system. In addition, the roles of ET-1 for morphology and proliferation on melanocytes were evaluated in different culture media. We suggest that ET-1 increases dendricity and proliferation of melanocytes, and that its dendrite-inducing effect and mitogenic effect are regulated independently.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.10
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• pp.1503-1509
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• 2007

Endothelin-1 (ET-1) is an important factor in regulation of cardiovascular tone in humans and mammals, but the biological function of ET-1 in the avian vascular system has not been determined. The purpose of this study was to characterize the role of endogenous ET-1 in the vascular system of poultry by investigating the effect of endothelin A receptor ($ET_AR$) antagonist BQ123 on the femoral artery pressure (FAP) and the pulmonary artery pressure (PAP) in broiler chickens. First, we found that plasma and lung homogenate ET-1 levels were both increased with age over the seven weeks life cyccle of broiler chickens. Second, 60 min after intravenous injection, BQ123 ($0.4{\mu}g\;kg^{-1}$ and $2.0{\mu}g\;kg^{-1}$, respectively) induced a significant reduction in FAP and PAP (p<0.05). Third, chronic infusion of BQ123 ($2.0{\mu}g\;kg^{-1}$ each time, two times a day) into abdominal cavities led to significant decrease in systolic pressure of the femoral (p<0.05) and pulmonary arteries (p<0.01) in broiler chickens at 7 and 14 days after treatment. Taken together, the $ET_AR$ antagonist BQ123 lead to a significant reduction of FAP and PAP, which suggests that endogenous ET-1 may be involved in the maintenance and regulation of systemic and pulmonary pressure in broiler chickens.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.119-123
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• 2001

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.92-92
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• 1997

Stereotaxic apparatus를 이용하여 흰쥐의 두개골을 천공하여 periaqueductal gray matter에 정확히 cannula를 삽입하여 1일 이상의 방치후 여기로 약물을 투여하여 일군의 동물들은 행동의 변화를 관찰하고, 일군의 동물들은 경동맥에서의 혈압과 심박수의 변화를 관찰한다. 결과: ET-1에 의해 유발된 barrel-rolling은 NMDA receptor-selective antagonist인 MK-801에 의해 유의성있게 억제되었으며, NOS antagonist인 L-NAME과 NO scavenger인 Hemoglobin에 의해서도 유의성 있게 억제되었다.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.210-222
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• 2000

Background: Endothelin(ET) is the most potent vasoconstrictor and bronchoconstrictor. The plasma ET-1 level is elevated in patients with acute pulmonary thromboembolism(APTE). This finding suggest that ET-1 may be an important mediator in the cardiopulmonary derangement of APTE. But whether ET-1 is a pathogenic mediator or a simple marker of APTE is not known. The role of ET-1 in the pathogenesis of cardiopulmonary dysfunction in APTE(delete) was investigated through an evaluation of the effects of $ET_A$-receptor antagonist on APTE. The increase in local levels of preproET-1 mRNA and ET-1 peptide in the embolized lung was also demonstrated. Methods: In a canine autologous blood clot pulmonary embolism model, $ET_A$-receptor antagonist(10 mg/kg intravenously, n=6) was administered one hour after the onset of the embolism. Hemodynamic measurements, blood gas tensions and plasma levels of ET-1 immunoreactivity in this treatment group were compared with those in the control group(n=5). After the experiment., preproET-1 mRNA expression(using Northern blot analysis) and the distribution of ET-1(by immunohistochemical analysis) in the lung tissues were examined. Results: The increases in pulmonary arterial pressure and pulmonary vascular resistance of the treatment group were less than those of the control group. Decrease in cardiac output was also less in the treatment group. Complications such as systemic arterial hypotension and hypoxemia did not occur with the administration of $ET_A$-receptor antagonist The plasma level of ET-1 like(ED: what does 'like' mean?) immunoreactivity was increased after embolization in both groups but was significantly higher in the treatment group. The preproET-1 mRNA and ET-1 peptide expressions were increased in the embolized lung. Conclusion: ET-1 synthesis increases with embolization in the lung and may plays play an important role in the pathophysiology of cardiopulmonary derangement of APTE. Furthermore, $ET_A$-receptor antagonist attenuates cardiopulmonary alterations seen in APTE, suggesting a potential benefit of this therapy.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.689-695
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• 2009

Purpose : To examine the effect of bosentan, a dual endothelin receptor (ER) antagonist, on the development of monocrotaline (MCT)-induced pulmonary hypertension in rats by especially focusing on the pulmonary vascular morphology changes. Methods : Sprague-Dawley rats were treated as follows: controls received a subcutaneous saline injection, MCT-treated rats received a subcutaneous MCT injection, and bosentan-treated rats received a MCT injection followed by treatment with bosentan (20 mg/kg/day). To assess the effects of ER blockade on the time course, the animals were exsanguinated, and their hearts and lungs were dissected after 7, 14, or 28 days. Results : The mean body weights of the MCT- and bosentan-treated rats were significantly lower than that of the control rats on days 7, 14, and 28. Bosentan administration significantly inhibited the progression of right ventricular hypertrophy on day 28 (right ventricle/[left ventricle＋septum]: $0.71{\pm}0.10$ in MCT-treated rats vs. $0.49{\pm}0.09$ in bosentan-treated rats; P<0.05). Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan-treated rats on day 28 ($49.96{\pm}10.06%$ in MCT-treated rats vs. $47.09{\pm}10.48%$ in bosentan-treated rats; P<0.05). In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on days 14 and 28. Conclusion : Bosentan administration in intermediate doses exerts inhibitory effects on lung vascular hypertrophy and right ventricular hypertrophy during the development of MCT-induced pulmonary hypertension in rats.

• Tuberculosis and Respiratory Diseases
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• v.67 no.4
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• pp.275-280
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• 2009

Interstitial lung disease (ILD) is a group of diseases characterized by pulmonary interstitial inflammation. Finally the inflammation results in pulmonary fibrosis and impairment of oxygen transportation. The causes of idiopathic interstitial pneumonia (IIP) are unknown. Diagnosis of IIP is not easy, especially distinguising between nonspecific interstitial pneumonia and usual interstitial pneumonia (UIP). First line treatments of IIP include corticosteroids and immune modulators, which have limited effect. Currently, several drugs are being researched to prevent and treat fibrosis. Newer drugs that may useful to treat pulmonary fibrosis include endothelin receptor antagonist, recombinant soluble TNF receptor antagonist, and cotrimoxazole. The causes of IIP are largely unknown, treatment is not specific, and prognosis is poor. Recent studies are underway to investigate the pathogenesis and treatment of IIP and pulmonary fibrosis. As the pathogenesis of IIP is elucidated, better treatments will emerge.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.201-209
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• 2014

The present study was designed to investigate the efficacy of selective $ET_A$ receptor antagonist, ambrisentan on hyperhomocysteinemia-induced experimental vascular dementia. L-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia in male rats. Ambrisentan was administered to L-methionine-treated effect rats for 4 weeks (starting from $5^{th}$ to $8^{th}$ week of L-methionine treatment). On $52^{nd}$ day onward, the animals were exposed to the Morris water maze (MWM) for testing their learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. L-methionine-treated animals showed significant learning and memory impairment, endothelial dysfunction, decrease in/serum nitrite/nitrate and brain GSH levels along with an increase in brain TBARS levels and AChE activity. Ambrisentan significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. These effects were comparable to that of donepezil serving as positive control. It is concluded that ambrisentan, a selective $ET_A$ receptor antagonist may be considered as a potential pharmacological agent for the management of hyperhomocysteinemia-induced vascular dementia.