No abstract available.
Endothelins* ; Receptors, Endothelin*

To investigate the effect of endothelin on intracellular free calcium ([Ca(2+)]i) mobilization and the existence of the endothelin receptor in cultured bovine corneal endothelial cells(BCEC), endothelin-1(ET-1) -induced [Ca(2+)]i increase was measuredby using calcium sensitive indicator, fura-2/AM, and the studies on its desensitizaton and receptor antagonists were also performed. ET-1 increased [Ca(2+)]i in a concentration-dependent manner(10(-9)M-10(-5)M) and ET-1 -unduced [Ca(2+)]i transient increase was significantly ingibited (~50%) by the pretreatment with EGTA for 1 min. Similarly, neomycin also attenuated ET-1 -unduced [Ca(2+)]i transient increase in a concentration-dependent mannet. Desensitizatin study with successive treatment of ET-1 and ET-3, and the experiments of antagonists(BQ-610 for the ET(A) receptor and BQ-788 for the ET(B) receptor) showed the presence of ET(B) receptor in BCEC. In addition, ET-1(10(-6)M) accumulated inositol trisphosphate about two folds (310+/-6.8 cpm) comparing to control(154+/-11.6 cpm) and this accumulation was significantly inhibited by the treatment with neomycin (187+/-28 cpm). These results suggest that endothelin-induced calcium mobilization is receptor-mediated response and TE(B) receptor exists in BCEC.
Calcium* ; Egtazic Acid ; Endothelins ; Endothelium, Corneal* ; Inositol ; Neomycin ; Receptors, Endothelin

In systemic sclerosis, digital ulcers and gangrene are somewhat common clinical characteristics of obliterative vasculopathy. These manifestations increase morbidities, such as pain, infections, and acroosteolysis. However, patient responses to the appropriate treatments are often inadequate. We treated a patient with systemic sclerosis who had a refractory digital ulcer and gangrene with bosentan, an endothelin receptor antagonist, and observed improvement. Here we systematically review this case.
Acro-Osteolysis ; Gangrene* ; Humans ; Receptors, Endothelin ; Scleroderma, Systemic* ; Ulcer*

OBJECTIVE: To investigate the roles of ET in the regulation of peripheral vascular tone, we studied the effect of hyperlipidemia on vascular responsiveness in femoral arteries from rabbits with control groups of rabbits and test groups receiving a hyperlipidemic diet. MATERIALS AND METHODS: New Zealand Whites were anesthetized with pentobabital and killed by exsanguination from the femoral arteries. Arteries which were suspended on muscle chambers at their optimal length for contractile properties, were examined. RESULTS: 1. After 14-16 weeks of cholesterol-rich diet, plasma cholestrol and HDL levels were significantly higher in the hyperlipidemic rabbits than in the control rabbits. There was no significant difference in the triglyceride levels between the two groups. 2. The contractions caused by 60 mM KCI in the femoral arterial strips were significantly augmented (P<0.01). The contractile responses to phenylephrine or angiotensin II were also augmented, whereas 5-hydroxytryptamine or U46619- induced contraction was not affected by the hyperlipidemic diet. 3. In control rabbits, ET-1 and ET- 2 contracted femoral arteries in a concentraction-dependent manner, whereas sarafotoxin S6c and IRL 1620 had no effect. 4. Contractions caused by ET-1 and ET-2 were significantly diminished by hyperlipidemia. 5. ET-1-induced concentration-response curves were inhibited by BQ-610, but not affected by BQ-788 in the femoral arterial strips from control and hyperlipidemic rabbits. CONCLUSIONS: These results suggest that ET is involved in the regulation of vascular tone in peripheral arteries and ETA receptor subtypes are mainly present in rabbit femoral arteries. Further more, ET-induced contraction is attenuated in hyperlipidemic rabbit, and the attenuated responses might be caused at least in part by the alteration of ET receptors (e.g. desensitization).
Angiotensin II ; Arteries ; Diet ; Endothelin-2 ; Endothelins* ; Exsanguination ; Femoral Artery* ; Hyperlipidemias ; New Zealand ; Phenylephrine ; Plasma ; Rabbits* ; Receptors, Endothelin ; Serotonin ; Triglycerides

Endothelin-1 (ET-1) is unequivocally elevated in the kidney with ischemic acute renal failure (ARF), whereas ET receptors (ET(A)R and ET(B)R) 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-1 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 ET(A)R mRNA and protein. Most of the increased immunoreactive ET-1 and ET(A)R were localized in damaged tubules. Neither the expression of ET(B)R mRNA nor the abundance and immunoreactive level of ET(B)R protein were changed. The findings suggest that the individual components of the renal ET system are differentially regulated in cisplatin-induced nephrotoxic ARF.
Acute Kidney Injury ; Animals ; Blotting, Western ; Cisplatin ; Endothelin-1 ; Endothelins ; Immunohistochemistry ; Kidney ; Mice ; Receptors, Endothelin ; RNA, Messenger

The presence of severe pulmonary arterial hypertension (PAH) in patients with atrial septal defect (ASD) is still thought to preclude shunt closure, although there are several reports of good clinical outcomes after vasodilator therapy. We report the case of a young woman with ASD and severe PAH who was able to successfully undergo percutaneous shunt closure following 1 year use of the oral endothelin receptor antagonist, bosentan.
Female ; Heart Septal Defects, Atrial* ; Humans ; Hypertension, Pulmonary* ; Receptors, Endothelin* ; Sulfonamides

Endothelin (ET) is a peptide released by vascular endothelial cells. Except for the potent vasoconstrictor function it plays an important physiological role in tissue differentiation and development, cell proliferation and hormone production. Investigation of the role of ET axis in a variety of tumors such as prostatic, cervical, breast carcinoma has provided evidences of its importance in cancer, recently. Data suggest that multiple functions of the ET axis have associations with mitogenesis, apoptosis inhibition, angiogenesis, and activation of proto-oncogene. The ET axis relates to invasiveness, osteoblast function, and metastatic cancer pain in advanced prostate cancer.
Animals ; Apoptosis ; Endothelins ; physiology ; Humans ; Male ; Mice ; Prostatic Neoplasms ; pathology ; physiopathology ; Receptors, Endothelin ; physiology

BACKGROUND: The purpose of this study was to investigate the mechanism of endothelium-dependent and independent responses to endothelins (ETs) in porcine coronary artery. METHODS: The vascular rings of left anterior descending artery or left circumflex artery from 7 pigs were suspended in conventional organ chambers for the measurement of isometric force. To evaluate relaxation responses, vascular rings with endothelium were exposed to ET-1 and ET-3. To evaluate contraction responses, vascular rings with and without endothelium were exposed to ET-1 and ET-3 in the presence or absence of BQ 123 (ET(A) receptor antagonist) or TAK-044 (ET(A) and ET(B) receptor antagonist). RESULTS: Transient relaxation responses of vascular rings occurred after exposure of ET-1 and ET-3. These transient responses disappeared after preincubation with N-nitro-L arginine. There was an increased contractions of vascular rings according to increasing concentration of ET-1 and ET-3. The initial responses were enhanced in vascular rings without endothelium in ET-1 and ET-3. In vascular rings with endothelium, the contraction responses were more reduced in vascular rings with preincubation of BQ 123 than in vascular rings without BQ 123 in ET-1. In vascular rings without endothelium, the contraction responses were more reduced in vascular rings with preincubation of TAK-044 than in vascular rings without TAK-044 in ET-1. CONCLUSION: ET(B) receptor on the endothelium might mediate the transient vasodilator responses to ET-1 and ET-3 through release of nitric oxide in porcine coronary artery. ET(A) and ET(B) receptor on vascular smooth muscle cells might mediate vasoconstrictor responses to ETs.
Arginine ; Arteries ; Coronary Vessels* ; Endothelins* ; Endothelium ; Muscle, Smooth, Vascular ; Nitric Oxide ; Receptors, Endothelin ; Relaxation ; Swine

Humans ; Liver ; cytology ; metabolism ; Liver Diseases ; metabolism ; pathology ; therapy ; Receptors, Angiotensin ; metabolism ; Receptors, Cell Surface ; metabolism ; Receptors, Endothelin ; metabolism ; Receptors, Vasopressin ; metabolism

BACKGROUND AND OBJECTIVES: Endothelin (ET)-1, a potent endothelium-derived vasoconstrictor peptide, has a potential pathophysiologic role in pulmonary hypertension. Bosentan, a dual ET receptor (ET(A)/ET(B)) antagonist, is efficacious in treatment of pulmonary hypertension. The objectives of this study were to investigate the expression of ET-1 and ET receptor A (ERA) genes and to evaluate the effect of bosentan in monocrotaline (MCT)-induced pulmonary hypertension. MATERIALS AND METHODS: Four-week-old male Sprague-Dawley rats were treated as follows: control (n=36), subcutaneous (sc) injection of saline; MCT (n=36), sc injection of MCT (60 mg/kg); and bosentan (n=36), sc injection of MCT (60 mg/kg) plus 25 mg/kg/day bosentan orally. RESULTS: Serum ET-1 concentrations in the MCT group were higher than the control group on day 28 and 42. Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan group on day 28 and 42. In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on day 14, 28 and 42. The levels of ET-1 and ERA gene expression were significantly increased in the MCT group compared with control group on day 5, and bosentan decreased the expression of ET-1 on day 5. CONCLUSION: ET-1 contributes to the progression of cardiopulmonary pathology in rats with MCT-induced pulmonary hypertension. Administration of bosentan reduced ET-1 gene expression in MCT-induced pulmonary hypertension in rats.
Animals ; Arteries ; Endothelin-1 ; Endothelins ; Gene Expression ; Humans ; Hypertension, Pulmonary ; Male ; Monocrotaline ; Pulmonary Artery ; Rats ; Rats, Sprague-Dawley ; Receptors, Endothelin ; Sulfonamides