Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the regulation of endothelin-1 (ET-1) production, cardiac catheterization was performed in young patients with congenital heart disease (27 +/- 5 months old, mean +/- SEM), and plasma levels of ET-1 in the inferior vena cava were measured by a sandwich-enzyme immunoassay. Plasma ET-1 levels of age-matched healthy controls were 1.55 +/- 0.07 pg/ml (n = 6). In patients with atrial septal defect [without pulmonary hypertension (PH)] who had volume but not pressure overload to the pulmonary circulation (PC), plasma ET-1 levels were significantly lower than in controls. In patients with PH due to ventricular septal defect (VSD) who had both volume and pressure overload to PC, the levels were significantly higher than in controls. In patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS), plasma ET-1 levels were significantly higher than in those with VSD, suggesting that ET-1 production is also augmented by pulmonary congestion. The present findings suggest that ET-1 production is increased by pressure overload to PC but decreased by volume overload to PC.
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PMID:Influence of pulmonary blood pressure and flow on endothelin-1 production in humans. 858 35

The effects of experimental chronic heart failure (CHF) on the density and affinity for endothelin-1 (ET-1) binding was studied in the rat heart. Because it has been reported that ET-1 binding sites on cultured cardiocytes are downregulated by pretreatment with ET-1, we also studied the plasma concentrations of ET-1 in rats with CHF. Three weeks after ligation of the left coronary artery, rats developed chronic heart failure (CHF rats). The plasma concentrations of ET-1, as measured by a sandwich-enzyme immunoassay, were significantly higher in CHF rats than in sham-operated rats [4.80 +/- 0.33 vs. 0.91 +/- 0.11 (mean +/- SEM) pg/ml; p < 0.01]. [125I]ET-1 binding experiments on rat cardiac membranes revealed that the binding site density (Bmax) was significantly higher in the CHF rats than in the sham-operated rats (243.0 +/- 20.0 vs. 154.8 +/- 17.4 fmol/mg protein; p < 0.05), whereas the values for the dissociation constant (Kd) were not different between the two groups (28.7 +/- 7.0 vs. 29.8 +/- 1.9 pM). Therefore, in the CHF rats, although plasma concentrations of ET-1 were elevated, the density of myocardial ET receptors was increased. Because ET-1 has potent inotropic and hypertrophic effects on cardiac myocytes, it is suggested that the effects of endogenous ET-1 in the heart are different between the CHF rats and the sham-operated rats.
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PMID:Increased endothelin-1 binding sites in the cardiac membranes in rats with chronic heart failure. 858 42

The purpose of this study was to examine the effects of endothelin receptor inhibition on cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP). Structure and mechanics of cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP that were either untreated or treated for 3 months with bosentan, an inhibitor of endothelin receptors (100 mg/kg per day). We measured pressure, external diameter, and cross-sectional area of the vessel wall (histologically) in maximally dilated (EDTA) arterioles on the cerebrum. Bosentan reduced but did not normalize arteriolar mean pressure (103 +/- 3 and 81 +/- 5 mm Hg in untreated and treated SHRSP versus 51 +/- 4 mm Hg in WKY, P < .05; mean +/- SEM) and pulse pressure (40 +/- 2 and 33 +/- 2 mm Hg in untreated and treated SHRSP versus 25 +/- 3 mm Hg in WKY, P < .05) in SHRSP. Cross-sectional area of the vessel wall (CSA) was increased in untreated SHRSP (1627 +/- 173 microm2), and CSA in treated SHRSP (1287 +/- 78 microm2) was similar to that in WKY (1299 +/- 65 microm2). Bosentan had no effect on reductions in external diameter (remodeling) of cerebral arterioles (104 +/- 7 and 96 +/- 4 microm in untreated and treated SHRSP compared with 126 +/- 7 microm in WKY, P < .05). Stress-strain curves indicate that bosentan had no significant effect on distensibility of arterioles on the cerebrum in SHRSP. The results suggest that endothelin-1 may contribute to the development of hypertrophy, but not remodeling or changes in distensibility, of cerebral arterioles in SHRSP.
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PMID:Effects of endothelin receptor inhibition on cerebral arterioles in hypertensive rats. 861 42

Levels of calcitonin gene-related peptide (CGRP), a vasodilator peptide present in nerves and airway endocrine cells of the rat respiratory tract, are increased in hypoxic lung and decreased in plasma, suggesting impaired CGRP release. We wanted to determine whether there was an adaptive functional response to reduced CGRP levels in hypoxia. Density of binding sites for CGRP were compared with its vascular actions following hypoxia, and with binding following administration of the sensory neurotoxin capsaicin to deplete neural CGRP. Autoradiography of lung sections incubated with 125I-labelled CGRP and other vasoactive peptides was used to quantify their binding sites, in male Wistar rats exposed to periods of hypoxia (inspiratory oxygen fraction (FI,O2) = 0.1) ranging 0-10 days (n = 5 each), in controls, and in rats treated neonatally with capsaicin. Relaxation to CGRP was compared in pulmonary artery of control and hypoxic rats. CGRP binding was seen in the vascular endothelium and was significantly elevated after 5 days of hypoxia (mean +/- SEM: control 4.6 +/- 0.4 versus hypoxic 16.6 +/- 2.4 amol.mm-2). CGRP-induced (5 x 10(-7)M) relaxation of pulmonary artery was reduced, compared with controls, following 8 and 21 days of hypoxia (mean +/- SEM) percentage of relaxation to phenylephrine: 78 +/- 3, 36 +/- 5 and 32 +/- 3, respectively) and was abolished by removal of endothelium. Capsaicin treatment also significantly elevated vascular CGRP binding. Atrial natriuretic peptide (ANP) binding levels were decreased in smooth muscle of all blood vessels after 7 days of hypoxia, but endothelin-1 (ET-1) and vasoactive intestinal peptide (VIP) binding was unchanged. We conclude that the vasodilator effects of CGRP are endothelium-dependent and, whilst they are reduced in hypoxic lung, this is not due to reduction in receptors, thereby implicating alterations in the nitric oxide guanylyl cyclase system. Furthermore, adaptive responses in some peptide binding sites occur in hypoxia, which may be due to changes in endogenous peptide levels.
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PMID:Decreased endothelium-dependent pulmonary vasodilator effect of calcitonin gene-related peptide in hypoxic rats contrasts with increased binding sites. 866 97

The growth response of aortic vascular smooth muscle cells (VSMCs) to chronic hypertension includes vascular hypertrophy. We have shown previously that angiotensin II positively regulates the expression of the human vascular smooth muscle (SM) alpha-actin gene. To further expand our understanding of vasoactive peptide-induced vascular hypertrophy, we studied endothelin-1 (ET-1) regulation of total protein synthesis and cytoskeletal gene expression in VSMCs. In a concentration-dependent manner ET-1 increased [3H] leucine incorporation by VSMCs (122.4 +/- 5.5%, mean +/- SEM, n = 5). ET-1 (0.1 microM) induced expression of SM alpha-actin mRNA as detected by Northern blot analysis. Also, ET-1 in a concentration-dependent manner (0.1 nM-0.1 microM) induced expression of the chloramphenicol acetyl transferase gene driven by 896 bp of the human SM alpha-actin promoter when transiently transfected into rat aortic VSMCs by the calcium phosphate method (141.2 +/- 9.8%, mean +/- SEM, n = 10). These data suggest that part of ET-1-induced increase in protein synthesis is achieved through transcriptional regulation of the SM alpha-actin gene via activation of cis-acting element(s) in the promoter. Such findings help elucidate the role of ET-1 in regulation of vascular growth.
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PMID:Endothelin-1 induces an increase in total protein synthesis and expression of the smooth muscle alpha-actin gene in vascular smooth muscle cells. 876 40

The endogenous release of the vasoactive peptides atrial natriuretic peptide and endothelin-1 may modify maternal haemodynamic responses to a rapid intravenous volume load used to prevent hypotension at elective Caesarean delivery under spinal anaesthesia. Twenty-two healthy pregnant women were examined during elective Caesarean section at term pregnancy. They were randomly assigned to receive either 2000 ml of Ringer lactate solution (crystalloid group) or 500 ml of 6% hydroxyethyl starch + 1000 ml of Ringer lactate solution (colloid group). The mean (SEM) concentration of atrial natriuretic peptide in plasma increased from 10.9 (1.5) to 24.7 (5.1) pmol.l-1 during crystalloid infusion and from 10.3 (1.4) to 28.2 (5.6) pmol.l-1 during colloid infusion. A slight decrease in endothelin-1 levels was found during colloid infusion. A significant increase in the release of atrial natriuretic peptide in response to volume load may decrease vascular tone and initiate diuresis, thereby attenuating the effect of volume load on blood pressure during elective Caesarean delivery.
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PMID:Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia. 888 64

The daily profiles of both the plasma level and the urinary excretion rate of endothelin-1 were examined in 13 healthy volunteers (9 males and 4 females, aged 22 +/- 1 [SEM]). Plasma endothelin-1 (PET) was measured after a one-hour recumbency every 6 hours at 8 a.m., 2 p.m., 8 p.m. and 2 a.m. and the urinary excretion rate of endothelin-1 (UET) was determined in the urine collected every 6 hours. PET was found to be quite stable throughout the day, being 1.57 +/- 0.25 pg/ml at 8 a.m., 1.88 +/- 0.21 at 2 p.m., 2.2 +/- 0.24 at 8 p.m. and 1.90 +/- 0.20 at 2 a.m. After a one-hour ambulation, PET showed no statistical difference. UET also remained unchanged for each 6-hour collecting period, measuring 4.61 +/- 0.69, 3.98 +/- 0.46, 4.63 +/- 0.73 and 3.42 +/- 0.49 ng/hr, respectively. The absence of any daily variations in either PET or UET thus suggests that apparently no specific considerations need be applied regarding the time of taking samples to measure the plasma and urinary endothelin-1.
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PMID:Minimal daily variations of plasma and urinary endothelin-1 in healthy subjects. 895 27

Whether the serum levels of endothelin, a vasoconstrictive peptide produced in the endothelial cell, increase in preeclamptic patients is still controversial. We performed immunohistochemical studies to observe the changes in endothelin-1 (ET-1) in preeclamptic kidney tissues. The monoclonal anti-human ET-1 antibody (Yamasa, Japan) and anti-von Willebrand factor (vWF, Dako, Denmark), a marker of endothelial cells, were used for the studies by the strepto-avidin-biotin peroxidase method (ABC-POD Kit, Wako, Japan). Twenty-nine patients and 12 normal controls were divided into four groups. The preeclamptic group included 14 patients diagnosed with preeclampsia by clinical symptoms of hypertension, proteinuria, and edema occurring in late pregnancy and as having preeclamptic nephropathy. They underwent renal biopsy 16.7 +/- 1.0 (mean +/- SEM) days after delivery. The nephrotic group comprised 10 normotensive nonpregnant patients with nephrotic-range proteinuria examined through biopsy before treatment (six cases of minimal change, two of focal segmental glomerulosclerosis, one of membranous nephropathy, and one of IgA nephropathy). The pregnant women with preexisting glomerular disease group included five pregnant women with normal renal function who were normotensive and had no increase in the amount of proteinuria throughout pregnancy. They underwent renal biopsy 10.8 +/- 2.9 days after delivery (two cases of membranous nephropathy, one of focal segmental glomerulosclerosis, one of thin basement membrane disease, and one of non-IgA mesangioproliferative glomerulonephritis). The normal kidney group comprised 12 healthy tissue samples taken from nephrectomized kidneys (five cases of renal cell carcinoma, one case of lipofibrosarcoma, and six cases of kidney transplant donors). In these four groups, ET-1 and vWF showed equally positive staining in small arteries. VWF also showed positive staining in arterioles and peritubular capillaries in all groups. Although the glomeruli showed positive staining with ET-1 along the capillary walls in the normal group and the nonpregnant nephrotic group, they showed very weak or negative results in the preeclamptic group. Moreover, gravida with underlying glomerular disease without superimposed preeclampsia also showed negative findings of ET-1 in the glomeruli. The glomeruli in the four groups showed positive findings, with vWF readings the same as in the controls. These results indicate that the production of ET-1 in the glomerular endothelial cells decreases in cases of both preeclampsia and normal pregnancy, and the condition may be caused by pregnancy itself.
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PMID:Immunohistochemical study of endothelin-1 in preeclamptic nephropathy. 904 Dec 9

A role for calcium channels in the regulation of surfactant secretion is suggested by the observation that endothelin-1-stimulated surfactant secretion is inhibited by calcium channel blockers. 1,4-Dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridi ne carboxylic acid methyl ester (Bay K 8644), a dihydropyridine derivative, stimulates voltage-dependent and non-voltage-dependent calcium channels in a number of cell types. This study demonstrates that Bay K 8644 increased phosphatidylcholine (PC) secretion in isolated lung epithelial type II cells in a time- and concentration-dependent manner with an EC50 of 100 +/- 8 nM (mean +/- SEM, N = 6). The secretagogue effect of Bay K 8644 was independently decreased in the absence of external calcium, or in the presence of nifedipine, a calcium channel antagonist, or inhibitors of protein kinase C (PKC). Bay K 8644 increased intracellular calcium from 130 +/- 8 to 230 +/- 14 nM (N = 6, P < 0.05), an effect that was blocked by nifedipine. Bay K 8644 also increased the membrane-associated PKC activity in a concentration-dependent manner. In the membranes from Bay K 8644-stimulated cells, the increase in calcium-dependent PKC was greater than that in the calcium-independent PKC, suggesting preferential translocation of calcium-dependent PKC to the membranes. We suggest that both elevated calcium and activation of PKC are required for calcium agonist Bay K 8644-induced surfactant secretion in type II cells.
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PMID:Activation of protein kinase C by 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-py rid ine carboxylic acid methyl ester (Bay K 8644), a calcium channel agonist, in alveolar type II cells. 921 91

The endothelium-derived peptide endothelin-1 (ET-1) was evaluated in 14 male patients [mean age 52.74 years (SEM 1.10)] affected by coronary artery disease during a bicycle electrocardiographic stress test and dipyridamole echocardiogram. Both tests were performed before and after coronary revascularization. Fourteen healthy male subjects served as controls [mean age 53.21 years (SEM 1.63)]. Baseline plasma endothelin-1 levels were higher (P < 0.0001) in ischaemic patients [1.81 pg mL-1 (0.15, n = 14)] than in control subjects [0.61 pg mL-1 (0.03, n = 14)], but did not increase with exercise in both groups. Similar results were obtained with dipyridamole infusion. Endothelin-1 levels significantly decreased after coronary revascularization [before: mean 1.81 pg mL-1 (SEM 0.15, n = 14); after: mean 1.16 pg mL-1 (SEM 0.11), P < 0.002], without changes in the peptide response to both tests. In conclusion, elevated plasma endothelin-1 concentrations were found in patients with stable angina compared with non-ischaemic subjects. No changes were observed during exercise or dipyridamole infusion in both groups. Coronary revascularization was followed by a significant decrease in plasma endothelin-1 levels.
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PMID:Plasma endothelin-1 levels during transient acute myocardial ischaemia in men: effects of coronary revascularization. 922 34


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