• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.149-153
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• 2008

Endothelin-1 (ET-1) is unequivocally elevated in the kidney with ischemic acute renal failure (ARF), whereas ET receptors ($ET_AR$ and $ET_BR$) are variably expressed. Although renal functional and structural changes are similar between ischemic and nephrotoxic ARF, there are few reports on the alteration in the ET system in nephrotoxic ARF. This study was, therefore, undertaken to investigate changes in renal expression of ET-l and its receptors in nephrotoxic ARF induced by cisplatin. Mice were intraperitoneally injected with 16 mg of cisplatin/kg at a single dose, and the expression of mRNA and protein was then quantified by real-time RT-PCR and Western blot, respectively. Immunohistochemistry was conducted for localization. Three days after treatment, ET-1 transcript in cisplatin-treated mice was thirteen times higher than that in controls, whereas ET-1 peptide was increased by 1.5-fold. Cisplatin caused a 2-fold increase in the levels of ETAR mRNA and protein. Most of the increased immunoreactive ET-1 and ETAR were localized in damaged tubules. Neither the expression of ETBR mRNA nor the abundance and immunoreactive level of ETBR protein were changed. The findings suggest that the individual components of the renal ET system are differentially regulated in cisplatin-induced nephrotoxic ARF.

• Sleep Medicine and Psychophysiology
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• v.17 no.2
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• pp.69-74
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• 2010

Obstructive sleep apnea syndrome is associated with significant cardiovascular morbidity and increased mortality. However, it was controversial whether obstructive sleep apnea syndrome could cause pulmonary hypertension. The controversy was resolved by several studies that have shown pulmonary hypertension in 20% to 40% of patients with obstructive sleep apnea syndrome without underlying other cardiopulmonary diseases and reductions in pulmonary arterial pressure in patients with obstructive sleep apnea syndrome after treatment with nocturnal continuous positive airway pressure. Recent studies provide strong evidence for endothelial dysfunction in obstructive sleep apnea syndrome and pulmonary hypertension. Endothelin-1 is a 21 amino acid peptide with diverse biologic activity such as highly potent vasoconstrictor and mitogen regulator that may play a key role in obstructive sleep ap-nea syndrome and pulmonary hypertension. Continuous positive airway pressure therapy is moderately effective in reducing pulmonary arterial pressure. Further researches are needed to assess the therapeutic efficacy of pharmacologic therapy with agents that inhibit the action of endothelin-1 in obstructive sleep apnea syndrome patients with pulmonary hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.343-347
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• 2006

The present study was designed to investigate the effects renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and local natriuretic peptide (NP) system for glomerulopathy induced in the experimental bilateral ureteral obstructive rats. Sprague-Dawley male rats ($200{\sim}220g$ body weight) were bilaterally obstructed by ligation of the proximal ureters for 24 hours. Control rats were treated in the same ways, except that no ligature was made. The glomeruli were isolated from cortex by graded sieve methods, and the mRNA expressions of local renin-angiotensin system (RAS), aldosterone synthase (CYP11B2), endothelin-1 (ET-1) and NP system were determined by real-time polymerase chain reaction. Following the bilateral ureteral obstruction, the mRNA expressions of renin, angiotensin converting enzyme 1 as well as ET-1 were increased, while that of angiotensin converting enzyme 2 was not changed. The expressions of CYP11B2 and angiotensin II receptors were not changed. C-type natriuretic peptide (CNP) expression was increased, while its receptors (natriuretic peptide receptor-B) were not changed. We suggest that the upregulation of local RAS and ET playa role in the progressive glomerular injury, and that the enhanced CNP activity also plays a compensatory role in obstructive uropathy in the glomerulus.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1114-1124
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• 1997

Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.223-228
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• 2010

The collecting duct endothelin (ET) system, which involves ET-1 and its two receptors, may play a role in the regulation of renal sodium in association with the nitric oxide synthase (NOS) system. We determined whether sodium retention is associated with changes in the endothelin and NOS systems at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndromes. On day 7 after puromycin aminonucleoside (PAN) injection, urinary sodium excretion was decreased, ascites had developed, and there was a positive sodium balance. ET-1 mRNA expression was increased in the inner medulla of the kidney, whereas protein expression of ET receptor type B ($ET_BR$) was unchanged. The expression of neuronal NOS (nNOS) was decreased in the inner medulla. On day 14, urinary sodium excretion was unchanged compared with controls. The expression of $ET_BR$ increased, while nNOS expression in the inner medulla was comparable to controls. These findings suggest that decreased nNOS plays a role in the development of sodium retention in the nephrotic syndrome. Recovery of nNOS and increased renal $ET_BR$ synthesis may promote sodium excretion in later stages of the nephrotic syndrome (on day 14).

• 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.

• Journal of Oral Medicine and Pain
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• v.26 no.4
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• pp.319-329
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• 2001

Endothelin-1 (ET-1) is a recently discovered potent vasoconstrictive peptide. It was first identified in vascular endothelial cells. ET-1 is a 21-amino acid peptide and elicits systemic effects such as stimulation of the production of atrial natriuretic peptide and release of aldosterone and corticosterone. In this study, to examine the role of ET-1 in the bone metabolism, effect of ET-1 on the proliferation and activity of osteoblastic cells was studied using HOS cells as osteoblast model. ET-1 dose-dependently increased the cell proliferation as determined by cell counting and MTT reduction assay after 48hr treatment. Alkaline phosphatase activity was inhibited by ET-1 and showed significant inhibition by 50 and 100 nM ET-1. ET-1 increased NBT reduction by HOS cells dose-dependently showing that ET-1 may increase the superoxide production by osteoblasts. Nitrite concentration in the media of HOS cell culture without cytokine stimulation was negligible and unaffected by ET-1 after 48hr treatment. Finally, after collection and concentration of conditioned media, gelatinase activity produced by HOS cells was determined by zymography. HOS cells can produce and secrete the gelatinase (gelatinase A type as determined by molecular weight of about 65,000) into culture media, however, ET-1 had no effect on the gelatinase activity. These findings suggest that ET-1 may have diverse effects on the proliferation and differentiation of osteoblasts, therefore, it may play an important role in bone metabolism.

• The Journal of Internal Korean Medicine
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• v.41 no.4
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• pp.553-562
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• 2020

Objective: To investigate the vasodilatory effect of Sipjeondaebo-tang by inhibiting RhoA activity in vascular cells during cold exposure. Methods: Human vascular endothelial cells and pericytes were pretreated with Sipjeondaebo-tang for 30 min, followed by incubation at 37 ℃ (control) or 25 ℃ (cold exposure) for 30 min. Activation of endothelin-1-mediated RhoA in pericytes was assessed by pretreating the cells with Sipjeondaebo-tang for 30 min, followed by incubation with endothelin-1 at 37 ℃ for 30 min. Western blotting was performed to measure the expression of active RhoA. Endothelin-1 and nitric oxide release from endothelial cells was examined with enzyme-linked immunosorbent assay kits. The formation of stress fibers and focal adhesion complexes was analyzed by immunocytochemistry. Results: Cold treatment activated RhoA in both pericytes and vascular endothelial cells, whereas Sipjeondaebo-tang treatment inhibited this activation. Sipjeondaebo-tang treatment also reversed the cold-mediated production of endothelin-1 and nitric oxide. Cold exposure promoted the formation of stress fibers and focal adhesion complexes by increasing the expression of phospho-focal adhesion complex kinase, whereas Sipjeondaebo-tang treatment suppressed this response. Conclusions: These findings suggested that Sipjeondaebo-tang inhibits cold-induced RhoA activation and its related pathway components, including endothelin-1 and nitric oxide, in vascular cells. Therefore, Sipjeondaebo-tang could be beneficial for the treatment of Raynaud's phenomenon.

• The Journal of Korean Physical Therapy
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• v.20 no.3
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• pp.53-59
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• 2008

Purpose: The non-receptor-type protein tyrosine kinase Syk (636 amino acids, 72 kDa) is ubiquitously expressed in hematopoietic stem cells and has been widely studied as a regulator and effector of B cell receptor signaling that occurs in processes such as differentiation, proliferation and apoptosis. However, the mechanism relating Syk and p38 mitogen-activated protein kinases (p38MAPK) by endothelin-1 (ET-1, 21 amino acids) stimulation in muscle cells, especially in the volume-dependent hypertensive state, remains unclear. Methods: In this study, we investigated the relationship between Syk and p38MAPK for isometric contraction and enzymatic activity by ET-1 from rat aortic smooth muscle cells and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive state rats (ADHR). Results: The systolic blood pressure was significantly increased in ADHR than in a control group of animals. ET-1 induced isometric contraction and phosphorylation of p38MAPK, which was increased in muscle strips from ADHR. Increased vasoconstriction and phosphorylation of p38MAPK induced by treatment with 30 nM ET-1 were inhibited by the use of 10${\mu}M$ SB203580, an inhibitor of p38MAPK from ADHR. Furthermore, ET-1 induced isometric contraction and phosphorylation of Syk and p38MAPK, which were increased in the aortic smooth muscle cells. Increased tension and phosphorylation of Syk and p38MAPK induced by ET-1 were inhibited by SB203580 from rat aortic smooth muscle cells. Conclusion: These results, suggest that the Syk activity affects ET-1-induced contraction through p38MAPK in smooth muscle cells and that the same pathway directly or indirectly is associated with volume dependent hypertension. The findings suggest the need to develop cardiovascular disease-specialized physical therapy.