Plasma Endothelin-1 Levels In Patients Research Articles

Plasma endothelin-1 levels in patients with rotator cuff tear: a case-control study

Plasma endothelin-1 levels in patients with rotator cuff tear: a case-control study

Plasma endothelin-1 levels in patients with resistant hypertension: effects of renal sympathetic denervation

Introduction: Resistant arterial hypertension (RHT) is defined as poor controlled blood pressure (BP) despite optimal doses of three or more antihypertensive agents, including a diuretic. In the development of RHT, hyperactivity of sympathetic (SNS) and renin–angiotensin–aldosterone (SRAA) systems are involved, and SNS is a potent stimulator of vasoactive endothelin-1 (ET-1) peptide. Renal sympathetic denervation (RSD) through disrupting renal afferent and efferent nerves attenuates SNS activity.Material and methods: We carried out pilot study investigating the effect of RSD on BP and plasma ET-1 levels in consecutive 9 RHT patients (7 male and 2 female, mean age of 56 ± 13.3).Results: After 12 months of the RSD, we observed a significant reduction of BP office, 24-h ambulatory BP monitoring (ABPM) (p < 0.05, respectively), and “non-dipping” pattern (from 55% to 35%) (p < 0.05). Moreover, RSD significantly decreased plasma ET-1 levels in both renal artery (at right from 21.8 ± 4.1 to 16.8 ± 2.9 pg/ml; p = 0.004; at left from 22.1 ± 3.7 to 18.9 ± 3.3 pg/ml; p = 0.02). We observed positive correlations between plasma renal arteries ET-1 levels and systolic BP values at ABPM [Global-SBP (r = 0.58; p < 0.01), Diurnal-SBP (r = 0.51; p < 0.03) and Nocturnal-SBP (r = 0.58; p < 0.01), respectively].Discussion: Our data confirmed the positive effects of RSD on BP values in patients with RHT, and showed a possible physio-pathological role of ET-1.KEY MESSAGESRSD is associated to a significant reduction of plasma ET-1 levels, representing an useful tool into reduction of BP in RHT patients.

Decreased endothelin-1 plasma levels in multiple sclerosis patients: a possible factor of vascular dysregulation?

BackgroundMultiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with possible involvement of vascular dysregulation secondary to endothelial dysfunction caused by destruction of the vessel wall. Vascular dysregulation leads to excessive vasoconstriction or insufficient vasodilatation, resulting in vasospasm mediated by endothelin-1 (ET-1), the most potent and long-lasting mediator. Vascular dysregulation can play an important role in the pathogenesis of some eye disorders and it has been hypothesized that it is a vascular risk factor for glaucomatous optic neuropathy. The aim of this study was to estimate endothelin-1 (ET-1) plasma levels in patients with MS.Material/MethodsThe MS group consisted of 39 patients (9 males, 30 females), mean age: 38.8±10.02 years, range: 22–62. The control group consisted of 27 healthy volunteers (3 males and 24 females), mean age: 37.4±10.88 years, range: 20–62; clinically, in a non-active stage of the disease. ET-1 plasma levels were measured using the Endothelin-1 ELISA Kit (Immuno-Biological Laboratories Co., Japan). Statistical analysis was performed with the nonparametric Mann-Whitney U test for independent groups.ResultsEndothelin-1 (ET-1) plasma levels were significantly lower in MS patients compared to healthy controls: mean value 0.55±0.44 pg/ml (146.05±118.27 fmol/ml) vs. 0.95±0.48 pg/ml (252.83±127.16 fmol/ml); P=0.012.ConclusionsSignificantly decreased ET-1 plasma levels in the MS patients could reflect the non-active disease at the time of ET-1 measurements or the effects of immunomodulatory treatment, but it cannot be excluded that decreased ET-1 plasma levels in these patients might result from vascular dysregulation.

Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

Decreased cerebral blood flow (CBF) may contribute to the pathology of multiple sclerosis (MS), but the underlying mechanism is unknown. We investigated whether the potent vasoconstrictor endothelin-1 (ET-1) is involved. We found that, compared with controls, plasma ET-1 levels in patients with MS were significantly elevated in blood drawn from the internal jugular vein and a peripheral vein. The jugular vein/peripheral vein ratio was 1.4 in patients with MS vs. 1.1 in control subjects, suggesting that, in MS, ET-1 is released from the brain to the cerebral circulation. Next, we performed ET-1 immunohistochemistry on postmortem white matter brain samples and found that the likely source of ET-1 release are reactive astrocytes in MS plaques. We then used arterial spin-labeling MRI to noninvasively measure CBF and assess the effect of the administration of the ET-1 antagonist bosentan. CBF was significantly lower in patients with MS than in control subjects and increased to control values after bosentan administration. These data demonstrate that reduced CBF in MS is mediated by ET-1, which is likely released in the cerebral circulation from reactive astrocytes in plaques. Restoring CBF by interfering with the ET-1 system warrants further investigation as a potential new therapeutic target for MS.

Pioglitazone induces regression and stabilization of coronary atherosclerotic plaques in patients with impaired glucose tolerance

To observe the effects of pioglitazone on coronary plaque area, plaque burden, serum high-sensitivity C-reactive protein, adiponectin and plasma endothelin-1 levels in patients with impaired glucose tolerance and coronary borderline lesions. Thirty patients were randomly divided into two groups: a pioglitazone group and a control group. The latter was administered placebo in addition to standard therapy; the former pioglitazone 15 mg/d in addition to standard therapy. Before treatment and 6 months later, left ventricular ejection fraction, serum lipid profile, high-sensitivity C-reactive protein, adiponectin and plasma endothelin-1 levels were detected. Coronary plaque area and plaque burden were examined using intravascular ultrasound. No significant differences were found in left ventricular ejection fraction and serum lipid levels pre- and post-trial. Compared with the control group, 6 months' treatment with pioglitazone significantly decreased coronary plaque burden (50.7 ± 11.1 vs. 64.1 ± 10.3%, P < 0.05), plaque area (6.22 ± 2.03 vs. 8.31 ± 4.29, P < 0.05), thin-cap fibroatheroma prevalence (11 vs. 22%, P < 0.05) and percentage of necrotic core area (16 ± 8 vs. 31 ± 7%, P < 0.05). Compared with the control group, serum high-sensitivity C-reactive protein and plasma endothelin-1 levels were significantly lower and adiponectin level significantly higher in patients in the pioglitazone group. Serum adiponectin level was negatively correlated with plasma endothelin-1 level and coronary plaque area (r = 0.739 and -0.431, respectively, both P < 0.05). Pioglitazone may induce regression and stabilization of coronary atherosclerotic plaques. The mechanisms might involve inhibition of inflammation, increase in adiponectin level and improvement in endothelial function.

E0394 The relationship between obstructive sleep apnea and endothelin-1 plasma levels in patients with coronary heart disease

ObjectiveObstructive sleep apnea (OSA) is an independent risk factor for cardiovascular morbidity and mortality. The mechanism is unknown, but recent studies provide evidence that endothelial dysfunction might contribute. So we...

Capillary dimension measured by computer-based digitalized image correlated with plasma endothelin-1 levels in patients with systemic sclerosis

Endothelial and vascular damage are main leading disability in systemic sclerosis (SSc). Raynaud's phenomenon is the early symptom that presents vascular damage. Nailfold capillaroscopy (NFC) is an easily accessible diagnostic tool in secondary Raynaud's phenomenon. Considering the endothelial damage, clinical manifestations, and plasma cytokines was compared with traditionally used NFC parameter for, which to observe the number of capillaries, deletions in 3 mm, apical limb width and the capillary width itself. We hypothesize that a computer-based NFC system can generate a new powerful parameter which predicts the capillary dimension. We investigated the relationship among the plasma endothelin-1 (ET-1), clinical manifestations and quantitative analysis of computerized NFC, and to assess the optimal method in SSc. The level of ET-1 in 60 SSc patients, 30 healthy, and 23 disease controls were measured by enzyme-linked immunosorbent assay (ELISA) kit. We present a significant difference in all parameters of NFC between SSc patients and control groups. ET-1 level was increased in patients with SSc. In SSc group, capillary dimension and loss of capillaries were strongly associated with digital ulceration (p < 0.01) and pulmonary hypertension (p < 0.05). Capillary dimension and ET-1 level was in correlation with skin-hardening grade, and was higher in SSc patients with pulmonary hypertension or digital ulcer. Capillary dimension showed strong correlation with the endothelin-1 in SSc, healthy and disease control groups. (Rs = 0.31/p < 0.05, Rs = 0.82/p < 0.001, Rs = 0.83/p < 0.001). The results suggest that computer-based microscopic analysis of NFC is a useful method that potentially provides information on organ involvement and plasma ET-1. Capillary dimension maybe a powerful parameter possibly applicable in outpatient clinic for assessing SSc patients.

This issue of Acta

This issue of Acta

Plasma endothelin-1 levels in patients with complex regional pain syndrome

The clinical characteristics of complex regional pain syndrome (CRPS) – spontaneous and stimulus-evoked pain, autonomic abnormalities, motor dysfunction, and trophic changes in the affected limb – are well known. However, its pathogenesis is unclear, and the diagnosis is often delayed, in part due to lack of objective laboratory tests. Endothelin-1 (ET-1) is a potent vasoconstrictor that has recently been shown to produce pain, allodynia, edema, and muscle weakness, as well as to exert a direct excitatory effect on nociceptive afferents. Furthermore, new evidence indicates that ET-1 is involved in various cancer- and non-cancer-related painful conditions. The aim of the present explorative study was to determine the ET-1 plasma levels in patients with CRPS in an attempt to identify a `laboratory marker' for CRPS and to search for evidence suggesting that ET-1 may be involved in the pathogenesis of CRPS. ET-1 plasma levels were determined in 20 severely affected CRPS patients, in eight patients with non-CRPS chronic painful conditions, and in 10 healthy volunteers. The results showed that there were no significant differences in ET-1 plasma levels between the three groups. We conclude that the plasma level of ET-1 cannot be regarded as a `marker' for CRPS. Yet, the possibility that ET-1 is involved in the pathophysiology of CRPS has not been excluded and deserves further investigation.

Plasma endothelin-1 levels and clinical correlates in patients with chronic heart failure

Background: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and patients with chronic heart failure (CHF) are reported to have high plasma ET-1 levels. The aim of this study was to investigate the relation between plasma ET-1 levels and clinical correlates in patients with CHF. The effects of maximal exercise on plasma ET-1 levels were also investigated. Methods: Plasma concentrations of ET-1, norepinephrine, and atrial and brain natriuretic peptide (ANP and BNP) both at rest and after maximal cardiopulmonary exercise test were determined in 100 patients with CHF (60 ± 12 years, New York Heart Association [NYHA] class I-III, left ventricular ejection fraction [LVEF] = 36 ± 8%, peak oxygen uptake [VO2] = 18.2 ± 5.0 mL/min/kg) and 27 controls. Results: Patients with NYHA class II and III CHF had higher ET-1 levels (controls, NYHA class I, II, III: 2.1 ± 0.6, 2.1 ± 1.0, 2.6 ± 0.9, 3.4 ± 0.8 pg/mL, analysis of variance P <.0001). Maximal exercise did not alter ET-1 levels in controls or in each CHF subgroup. When all CHF patients were analyzed together, cardiothoracic ratio (P <.01), peak VO2 (P <.001), plasma norepinephrine (P <.01), plasma ANP (P <.01), and plasma BNP (P <.001) were significantly related with resting ET-1 levels on univariate analysis. Multivariate analysis revealed peak VO2 and plasma BNP levels showed an independent and significant relationship with the resting plasma ET-1 levels. Conclusions: Resting ET-1 levels were increased in symptomatic patients with CHF, and maximal exercise did not increase ET-1 levels. Peak VO2 and plasma BNP levels were independently associated with resting plasma ET-1 levels in patients with CHF.

Plasma endothelin-1 levels in patients with biliary atresia: possible role in development of portal hypertension.

Biliary atresia (BA) is a severe neonatal liver disease characterized by progressive extrahepatic biliary tract and intrahepatic inflammatory process. Hepatic fibrosis and portal hypertension (PH) still occur despite the disappearance of jaundice following successful hepatic portoenterostomy. Endothelin-1 (ET-1) is a potent vasoconstrictor and has been reported to stimulate hepatic collagen synthesis. The aim of this study was to demonstrate the potential role of ET-1 in the pathogenesis of the progressive inflammation, fibrosis and PH in BA. Thirty pediatric patients with biliary atresia post-hepatic portoenterostomy and 12 healthy children were examined. The ET-1 level was determined by commercially available enzyme-linked immunosorbent assay kits. Endothelin-1 levels were elevated in the patients compared with those of the controls (5.45+/-3.34 vs. 2.74+/-2.17 pg/ml, P = 0.01). Moreover, patients with PH also had greater levels of ET-1 than those without PH (6.73+/-3.27 vs. 3.26+/-2.2 pg/ml, P = 0.004). Patients with abnormal transaminase enzymes had significantly higher ET-1 levels than those with normal enzymes (6.43+/-3.33 vs. 3.17+/-2.1 pg/ml, P = 0.01). In the jaundice-free group, endothelin-1 levels were elevated in the patients with PH compared with those without PH (5.93+/-2.15 vs. 2.88+/-2.1 pg/ml, P = 0.02). Our findings showed elevation of plasma ET-1 levels in patients with BA, especially in those with PH. ET-1 levels were also higher in patients with elevated transminase enzymes as well as in the jaundice-free group with PH. ET-1 might play a role in the pathogenesis of the progressive inflammation, fibrosis and PH in BA.

Extraocular Blood Flow and Endothelin-1 Plasma Levels in Patients with Multiple Sclerosis

In order to evaluate whether plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) are increased in patients with multiple sclerosis (MS) and whether these patients exhibit an ET-1-mediated vascular dysregulation, ET-1 plasma levels were measured in 30 patients with MS. Blood flow velocities in the ophthalmic artery, central retinal artery, central retinal vein, short lateral posterior ciliary artery, and short medial posterior ciliary artery were assessed in parallel. ET-1 plasma levels were significantly increased in MS patients when compared to sex- and age-matched healthy controls (2.0 ± 0.4 pg/ml, range 1.1–2.8 vs. 1.5 ± 0.2 pg/ml, range 0.9–2.0; p < 0.001). Moreover, the patients exhibited significant alterations of extraocular blood flow. The role of ET-1 in the inflammatory process remains to be clarified.

Intravenous nesiritide (human B-type natriuretic peptide) reduces plasma endothelin-1 levels in patients with decompensated congestive heart failure

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Evaluation of plasma endothelin-1 levels in patients with cerebral infarction.

Endothelin-1 (ET-1) is a vasoconstrictor peptide derived from endothelium. Many authors have shown that ischemic stroke is associated with elevated plasma ET-1 levels. Also, the present findings related to plasma ET-1 levels with clinical status, size of the infarction, location of the infarction, and prognosis of the cerebral infarction were contradictory. In this study, plasma ET-1 levels in 30 patients with cerebral infarction within 72 hours after the onset of focal neurologic deficit and at their seventh day postinfarction were measured by a microplate enzyme immunoassay. Thirty sex- and age-matched healthy subjects were accepted as a control group. The mean plasma ET-1 concentrations in patients on admission, in patients at day 7, and in control subjects were 1.93 +/- 1.79, 1.03 +/- 1.02, and 0.65 +/- 0.32 fmol/mL, respectively. The mean plasma ET-1 level of patients on admission was found to be significantly higher than in patients at day 7 and in control subjects (p < 0.05). No significant difference in ET-1 levels was observed between the patients at day 7 and control subjects. Furthermore, there was no correlation between plasma ET-1 concentration and size of infarction, location of infarction, degree of clinical neurologic deficit, or prognosis of cerebral infarction. It was concluded that plasma ET-1 levels shortly after ischemic stroke were increased, which may be associated with the acute-phase reaction of cerebral infarction and may have deleterious effects on development of neuronal injury.

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Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n=10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ETA and ETB, on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P<0.01, 3.9±1.4, 4.5±1.5, vs. 2.75±1.37pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ETA antagonist (BQ123) 30min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ETA receptors. ETA antagonists are indicated as potential anti-cancer agents. © 2001 Cancer Research Campaign http://www.bjcancer.com

Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism.

Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET A and ET B, on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 ± 1.4, 4.5 ± 1.5, vs. 2.75 ± 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET A antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET A receptors. ET A antagonists are indicated as potential anti-cancer agents. © 2001 Cancer Research Campaign http://www.bjcancer.com

The relation between plasma endothelin-1 levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy in patients with Type 2 diabetes mellitus

We evaluated the possible relation between plasma endothelin-1 (ET-1) levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy, including nephropathy, neuropathy, and retinopathy in patients with Type 2 diabetes and healthy control group. Sixty-eight (39 females and 29 males) patients with Type 2 diabetes and 14 (6 females and 8 males) healthy subjects were included in the study. Plasma ET-1 levels were found to be 10.46±1.24 pmol/l in the diabetic group, whereas 7.97±0.41 pmol/l in the control group, which was statistically significant ( P<.01). We also found elevated plasma ET-1 levels in patients with the least one microvascular complication when compared with the uncomplicated diabetes group ( P=.02). Moreover, plasma ET-1 levels of the uncomplicated group was higher than the control group ( P<.05). Plasma ET-1 levels were significantly elevated in hypertensive diabetics than normotensive diabetics ( t=2.58, P=.012). It was also found to be elevated in diabetic patients with diabetes duration of more than 10 years when compared with patients less than 10 years ( P=.02). These findings can be interpreted as the increased damage of microvascular complications in the disease process that may lead to elevated ET-1 levels. Mean plasma ET-1 levels in diabetic patients with a family history of diabetes was found to be higher than patients with no family history of diabetes. Genetical and environmental factors may have an effect on ET-1 level. We also studied the correlations of plasma ET-1 levels on age, sex, fasting blood glucose levels, treatment modalities HbA1c, hyperlipidemia, C-peptide, Body Mass Index, and smoking, but did not find any statistically significant difference. In conclusion, plasma ET-1 levels are well correlated with microangiopathy, hypertension, increased disease duration, and family history of diabetes, but poorly correlated with metabolic control, treatment modalities, age, sex, hyperlipidemia, obesity, and smoking.

Increased endothelin-1 plasma levels in patients with multiple sclerosis.

We tested the hypothesis that the plasma level of endothelin-1 (ET-1) is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of the most potent known vasoconstrictors. An increased level of endothelin could explain some of the vascular symptoms of these patients. A specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty patients with MS were compared to 20 age- and sex-pair-matched healthy subjects. The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease. The plasma ET-1 level is markedly and significantly increased in patients with MS. Neither the cause of such an increase nor the pathogenetic role is known.

Role of endothelin in the control of peripheral vascular tone in human hypertension.

Endothelins are potent 21 amino acid vasoconstrictor isopeptides produced in different vascular tissues, including vascular endothelium. Endothelin-1 is the main endothelin generated by the endothelium and probably the most important in the cardiovascular system. Endothelin-1 acts through specific receptors termed ET(A), represented only on smooth muscle cells and having the function of growth promotion and mediating contractions, and ET(B), located both on smooth muscle cells, where they evoke contractions, and on endothelial cells, inducing relaxation by production of the endothelium-derived relaxing factor nitric oxide. In physiological conditions endothelin-1 administration causes vasodilation and vasoconstriction at low and high concentrations, respectively. However, administration of mixed ET(A)/(B) receptor antagonists causes slight or absent vasodilation, indicating that the direct vasoconstrictor effect of the peptide is probably masked by ET(B)-induced NO-dependent vasodilation. In essential hypertensive patients, the activity of exogenous endothelin-1 is either increased, similar or decreased as compared to normotensive subjects, depending on which vascular district or scheme of administration is considered. But although available evidence does not indicate increased endothelin-1 plasma levels in patients with essential hypertension, simultaneous antagonism of ET(A)/(B) receptors causes a greater degree of vasodilation in hypertensives than in normotensive subjects. Moreover administration of a selective ET(B) receptor antagonist causes vasoconstriction in normotensive subjects and vasodilation in essential hypertensive patients. Finally, the vasodilating effect of a mixed ET(A)/(B) receptor antagonist is inversely related to NO availability. Taken together these findings suggest that essential hypertension is characterized by increased endothelin-1 vasoconstrictor tone. This alteration seems to be dependent on decreased endothelial ET(B)-mediated NO production attributable to impaired NO availability. In such conditions endothelial ET(B)-induced vasodilation no longer compensates for the direct classical endothelin vasoconstrictor effect mediated by smooth muscle cell ET(A) and ET(B) receptors. Therefore endothelin-1 could potentially be involved in the pathogenesis of essential hypertension or of its complications, and blockade of this system is a fascinating new target for therapeutic intervention in this disease.

Renal endothelin in heart failure and its relation to sodium excretion

Background Recent studies have shown that endothelin-1 (ET-1) antagonists increase sodium excretion and improve renal blood flow in experimental heart failure (HF). However, despite a number of investigations that have reported a significant increase in ET-1 plasma levels in patients with HF, it is still not known whether increased renal synthesis and urinary excretion of ET-1 occur. Our aim was to investigate renal ET-1 formation and its relation to sodium excretion in patients with HF. Methods One hundred forty-seven patients with HF, subdivided according to New York Heart Association (NYHA) functional classes, and 28 healthy controls were studied. ET-1 and big ET-1 were measured in plasma and in 24-hour urine by radioimmunoassay. Atrial and brain natriuretic peptide, arginine vasopressin, plasma renin activity, and hemodynamic variables were also investigated. Results Urinary ET-1 excretion was already increased in NYHA class II patients (P < .001 vs controls), whereas plasma ET-1 increased only in NYHA class III and IV patients (P < .001). In the 71 subjects who were not receiving diuretic treatment, urinary ET-1 was selected as the strongest predictor of sodium excretion by multivariate stepwise analysis. Conclusions Urinary ET-1 excretion increases in an earlier phase of HF than plasma ET-1 and appears to be closely correlated with sodium excretion, indicating renal ET-1 is a target for ET-1 antagonists in patients with HF. (Am Heart J 2000;140:617-23.)