Plasma Endothelin-1 In Patients Research Articles

Effect of three vertigo-stopping needles on neurohumor of patients with cervical vertigo: a controlled trial

ObjectiveTo observe the effect of three vertigo-stopping needles on the contents of neuropeptide Y (NPY), endothelin (ET) and calcitonin gene-related peptide (CGRP) in plasma of patients with cervical vertigo, and to explore its mechanism of treatment. MethodsOne hundred and eighty patients with cervical vertigo were divided into group A [acupuncture at Rényíng (▪ ST 9) and Fēngchí (▪ GB 20), and frontal line], group B [acupuncture at Jing jiāji (▪), GB 20 and Baihuì (▪ GV 20)] and group C [intravenous infusion with ligustrazine and oral administration with flunarizine] according to simple randomization, with 60 cases in each group. For the patients in group A and group B, the treatment was conducted once a day, and ten times were considered as one course of treatment. Two days were free of treatment between two courses, and two courses were needed. For the patients in group C, the treatment was conducted for fifteen days. The contents of NPY, ET and CGRP in plasma before and after treatment were detected in patients with cervical vertigo. ResultsThe contents of NPY in plasma of patients in the three groups after treatment were markedly lower than that before treatment (all P<0.01), and the differences were not statistically significant when compared the descending degrees among three groups (P>0.05). The contents of ET in plasma of patients in the three groups after treatment were markedly lower than that before treatment (P<0.05, P<0.01), the descending degree in group A was greater than that in group B and group C, and the difference was statistically significant (P<0.01, P<0.05); while the difference was not statistically significant when compared the descending degrees between group B and group C (P>0.05). The contents of CGRP in plasma of patients in the three groups after treatment were markedly higher than that before treatment (P<0.05, P<0.01), the increasing degree in group A was greater than that in group B and group C, and the difference was statistically significant (both P<0.05); while the difference was not statistically significant when compared the increasing degrees between group B and group C (P>0.05). ConclusionThree vertigo-stopping needles, acupuncture and medication can regulate the contents of NPY, ET and CGRP in plasma of patients with cervical vertigo, while three vertigo-stopping needles is significantly superior to acupuncture and medication in reducing ET and increasing CGRP.

March 2016 at a glance. Focus on right ventricular failure and acute heart failure

The right ventricle has been always neglected as a cause of heart failure (HF). It is difficult to study with imaging techniques and, even more, difficult to treat when failing. The statement in this issue of the journal about the management of acute right ventricular failure is therefore particularly welcome.1 All the aspects regarding the pathophysiology, assessment and treatment of this condition are outlined. With respect to epidemiology, Van Riet et al. have reviewed the studies reporting the prevalence of HF and left ventricular (LV) dysfunction in community-dwelling people. These were of 5.5% and 36.0%, respectively.2 A study of 37,308 Swedish men shows that adherence to a Mediterranean diet is associated with a lower risk of HF and of HF mortality, confirming and extending previous data.3-5 Cancer is an important comorbidity in HF.6 A long-term follow-up study in Denmark shows that the incidence of cancer is also increased by 24% in the patients with HF, compared with the subjects without HF, and patients with HF and cancer had the worst outcomes.7 With respect to prognosis, Demissei et al. have assessed the prognostic value of 48 biomarkers measured in the PROTECT trial. Forty-four biomarkers were associated with outcomes, but 42 had limited value. Multimarker models with blood urea nitrogen (BUN), chloride, IL-6, cTnI, sST-2 and VEGFR-1 had a much stronger prognostic value. With the exception of BUN and galectin-3, late measurements provided superior accuracy for 180 days mortality.8 The independent prognostic value of plasma endothelin-1 in patients with acute HF is shown in the ASCEND-HF database.9 Body mass index had a U-shaped relation with in-hospital mortality in the patients with acute HF in the ALARM-HF study but this relation was lost after adjustment for covariates such as comorbidities and HF treatment.10 The long-term effects of treatment with Algysil intramyocardial injections in patients with HF in the AUGMENT-HF trial are shown with a long-term improvement in all the parameters related with exercise capacity and further data regarding cardiac remodelling and events.11

Plasma Endothelin-1 in patients with atrial septal defect – the novel diagnostic indicator (RCD code: IV-2B.1)

Background: The study aimed to assess the level of plasma Endothelin-1 (ET-1) in patients before and after transcatheter closure of atrial septal defect (ASD) and to evaluate the usefulness of measuring ET-1 levels for the diagnosis and selection of candidates for ASD closure. Methods: 21 patients (11 F, 10 M), mean age 40.2 ± 11.9 years with pulmonary artery hypertension were enrolled for an attempt at ASD closure. A group of 19 healthy volunteers, (12 F, 7 M) mean age 39.2 ± 9.15 served as controls. All ASD patients underwent: clinical and echocardiographic study and cardiopulmonary exercise test. ET-1 levels were measured before and after closure. Whole blood was collected from femoral artery and vein and from pulmonary artery during cardiac catheterization. Results: ET-1 levels at peripheral artery and vein in ASD patients were significantly higher than in the volunteers (p<0.0001). The ASD subjects with highest ET-1 level presented the larger area of right ventricle and right atrium and higher pulmonary artery systolic pressure(p<0.05). The ASD subjects with lower ET-1 level demonstrated longer time of exercise and higher peak oxygen consumption (p<0.05). There was a decrease of ET-1 at peripheral artery (5.549 ± 5.32 vs. 1.92 ± 7.2; p<0.001) and at peripheral vein (4.012 ± 2.342 vs. 2.15 ± 1.15; p<0.001) within 48 hours after ASD closure, as compared to the baseline data. After 6 and 12 months farther drop in ET-1 level was observed. Conclusions: 1. The level of ET-1 in patients with ASD and pulmonary artery hypertension is elevated in compare to healthy subject. 2. The significant reduction of ET-1 level is observed after percutaneous closure of ASD. 3. Elevated level of ET-1 in patients with ASD is associated with right heart enlargement. 4. Measurements of ET-1 may be a supplemental diagnostic tool and may be helpful in establishing indications for defect closure.

Elevated level of plasma endothelin-1 in patients with atrial septal defect

BackgroundThe study aimed to assess the level of plasma Endothelin-1 (ET-1) in patients before and after transcatheter closure of atrial septal defect (ASD) and to evaluate the usefulness of measuring ET-1 levels for the diagnosis and selection of candidates for ASD closure.Methods80 patients (55 F, 25 M), mean age 42,2 ± 11,5 years were enrolled for an attempt at ASD closure. A group of 19 healthy volunteers, (12 F, 7 M) mean age 39.2 ± 9.15 served as controls. All ASD patients underwent: clinical and echocardiographic study and cardiopulmonary exercise test. ET-1 levels were measured before and after closure. Whole blood was collected from femoral artery and vein and from pulmonary artery during cardiac catheterization.ResultsET-1 levels at peripheral artery and vein in ASD patients were significantly higher than in the volunteers (p < 0.0001). The ASD subjects with highest ET-1 level presented the larger area of right ventricle and right atrium and higher pulmonary artery systolic pressure(p < 0.05). The ASD subjects with lower ET-1 level demonstrated longer time of exercise and higher peak oxygen consumption (p < 0.05). There was a decrease of ET-1 at peripheral artery (5.128 ± 8.8 vs. 2.22 ± 6.2; p < 0.001) and at peripheral vein (4.401 ± 3.33 vs. 2.05 ± 1.35; p < 0.001) within 48 hours after ASD closure, as compared to the baseline data. After 6 and 12 months farther drop in ET-1 level was observed.Conclusions1. The level of ET-1 in ASD patients is elevated in compare to healthy subject.2. The significant reduction of ET-1 level is observed after percutaneous closure of ASD.3. Elevated level of ET-1 in patients with ASD is associated with right heart enlargement.4. Measurements of ET-1 may be a supplemental diagnostic tool and may be helpful in establishing indications for defect closure.

Low levels of plasma endothelin-1 in patients with retinitis pigmentosa

The aim of this study was to elucidate the role of endothelin-1 (ET-1) in the pathophysiology of retinitis pigmentosa (RP). Plasma ET-1 levels and ophthalmic features in 50 RP patients were compared with those in 20 healthy-eye control subjects. Plasma ET-1 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit. Mean plasma ET-1 levels of RP patients (1.88 +/- 0.56 pg/mL) were significantly lower than those of control subjects (2.30 +/- 0.30 pg/mL, Mann-Whitney's U test; P < 0.01). However, ET-1 concentrations varied markedly in each patient. Among RP patients, a significant correlation of ET-1 concentrations was not observed in terms of its hereditary forms or other clinical factors. ET-1 may be important in the pathogenesis of RP, and measurement of its plasma concentrations may also contribute to additional insights into the retinal hemodynamics of RP.

The Effects of Xuan Yun Ning on Plasma Endothelin in Patients with Vertebrobasilar Ischemia

Objective To explore the effects of Xuan Yun Ning on the plasma endothelin in pafients with vertebrobasilar ischemia.Methods 60 cases of vertebrobasila ischemia were randomly recruited into a treatment group and a control group,with 30 cases in each group.The control group was treated with Nimodipin,and the treatment group was treated with Xuan Yun Ning plus Nimodipin.Another 30 healthy persons whose age is more than 40 years were recruited for a healthy control group without any treatment The alterations of plasma endothelin were measured by radiation immunological test in the treatment group,the control group,and the healthy control group.Results The elevated plasma endothelin was significantly decreased in treatment group than the control group and the healthy control group(P＜0.05).Conclusion Xuan Yun Ning improves the blood volume by lowering the level of plasma endothelin and thus treats patients with vertebrobasilar ischemia. Key words: Xuan Yun Ning; Vertebrobasilar ischemia; Endothelin

Dynamic and differential changes in myocardial and plasma endothelin in patients undergoing cardiopulmonary bypass

The bioactive peptide endothelin modulates left ventricular function by changing afterload, coronary vascular tone, and myocardial contractility. However, whether increased plasma endothelin levels observed in patients during and after coronary revascularization and cardiopulmonary bypass reflect actual myocardial interstitial levels are unknown. A microdialysis probe (outer diameter: 0.77 mm; length: 4 mm) was placed in the left ventricular apical midmyocardium in 20 patients and myocardial interstitial fluid was collected (2.5 microL/min) at baseline and up to 30 minutes after cardiopulmonary bypass. Myocardial interstitial and systemic arterial endothelin were measured by radioimmunoassay. Baseline myocardial interstitial endothelin was over 6-fold higher than plasma (20.11 +/- 2.07 vs 3.19 +/- 0.25 fmol/mL, P < .05). Plasma endothelin increased by 23% +/- 12% at 60 minutes of cardiopulmonary bypass whereas myocardial interstitial endothelin increased by 105% +/- 24%, P < .05), and this change was higher than in the plasma ( P < .05). Although no further change in plasma endothelin occurred during cardiopulmonary bypass, myocardial interstitial levels increased further after crossclamp removal (400% +/- 75%) and remained significantly higher than plasma at separation from cardiopulmonary bypass. The unique findings of this study were 2-fold: First, significant compartmentalization of endothelin exists within the human myocardium. Second, a significantly higher and temporally disparate change in myocardial interstitial endothelin occurs during and after cardiopulmonary bypass when compared with systemic levels. These dynamic changes in myocardial endothelin likely influence coronary vascular tone and contractility.

Plasma endothelin in patients with acute aortic disease

Purpose and background: We investigated the plasma levels of endothelin 1/2 in patients with acute symptoms relating to a known or newly diagnosed aortic aneurysm in order to investigate the possible role of peptides in the development of the disease. Methods: Endothelin 1/2 plasma levels were determined in patients admitted to the emergency unit with suspected acute aortic disease. The history, type of aneurysm, outcome and laboratory findings were determined and compared to endothelin 1/2 levels collected on admission. Results: In patients with ruptured aneurysm ( n=27) or acute aortic dissection ( n=18) the endothelin 1/2 median levels were higher 1.1 (25th and 75th quartile 0.7, 1.7) fmol/ml than in patients ( n=20) with pre-existing aneurysm 0.7 (0.4, 1.1) fmol/ml ( P=0.013). Patients who died had significantly higher endothelin levels 1.3 (0.8, 1.9) fmol/ml than the survivors 0.8 (0.5, 1.4) fmol/ml ( P=0.04). In a logistic regression analysis, only a higher blood pressure on admission was an independent predictor of survival. Conclusion: Endothelin 1/2 levels are elevated in patients with acute dissection or ruptured aneurysm, but they are not an independent predictor of survival.

Hepatic Localization of Endothelin-1 in Patients With Idiopathic Portal Hypertension and Cirrhosis of the Liver

Endothelin-1 (ET-1) may mediate increased resistance to hepatic sinusoidal blood flow. We evaluated the hepatic distribution of ET-1 in patients with idiopathic portal hypertension (IPH), in which liver architecture may be normal, and in patients with cirrhosis, in which distortion of hepatic sinusoidal architecture is prominent. Immunohistochemistry and in situ hybridization were used to localize ET-1 in hepatic tissue of patients with IPH and cirrhosis. ET-1 was measured in plasma from a peripheral vein, the hepatic vein, and the portal vein of patients with cirrhosis of the liver and controls. On immunohistochemistry and in situ hybridization, ET-1 was localized to periportal hepatocytes and sinusoidal cells in patients with IPH and cirrhosis. Minimal positive staining for ET-1 was observed in control livers. Plasma ET-1 levels were significantly greater in patients with cirrhosis than in controls. In patients with cirrhosis, ET-1 was greater in the hepatic vein compared with the portal vein. However, the level of plasma ET-1 in patients with cirrhosis did not correlate with either the presence of ascites or portacaval pressure gradient. We conclude that in IPH, ET-1 is localized to sites in which it can modulate intrahepatic resistance. In late stages of cirrhosis, ET-1 may not modulate resistance. We speculate that vascular resistance in late stages of cirrhosis probably results from distortion of hepatic architecture.

Level of plasma endothelin and effect of chemotherapy on plasma endothelin in patients with lung cancer.

To detect the level of plasma endothelin (ET) in patients with lung cancer and effect of chemotherapy on it , and to investigate the role of ET in the development of lung cancer. Radioimmunoassay was available to detect the level of plasma ET in 30 cases of normal control subjects and 33 cases of patients with lung cancer before and after chemotherapy. The levels (197.49 +/-24.43ng/L and 200.68 +/-23.13ng/L) of plasma ET in squamous cell carcinoma and adenocarcinoma after chemotherapy were much lower than those (246.32+/-28.28ng/L and 243.91+/-25.75ng/L) before chemotherapy ( P < 0. 025 and P < 0. 01) , and all of the above were higher than that (168.43+/-21.54ng/L) in the control group ( P < 0. 01) .But the differences were not significant in the patients with small cell lung cancer ( P > 0. 05) . In staging , the levels of plasma ET in stage II-IV were higher than that in normal control group ( P < 0. 01) , and were lower after chemotherapy than those before ( P < 0. 01 or P < 0. 05) , but the differences in the four stages were not significant ( P > 0. 05) . ET may play an important role on growth and regulation in squamous cell carcinoma and adenocarcinoma , but it is not significant in small cell lung cancer. Chemotherapy can remarkably decrease the levels of plasma ET in squamous cell carcinoma and adenocarcinoma , but it may not do in small cell lung cancer. The elevation of plasma ET may be a clinical index in progressive lung cancer.

The origin of endothelin-1 in patients with severe preeclampsia

To determine the site of origin of increased concentrations of plasma endothelin-1 in patients with severe preeclampsia. Twelve patients with severe preeclampsia undergoing an indicated abdominal delivery had endothelin-1 levels measured from plasma specimens drawn from right and left uterine and antecubital veins before delivery and after placenta removal with uterine curettage. Twelve uncomplicated control patients undergoing abdominal delivery had endothelin-1 concentrations drawn by an identical protocol. Clinical staff members were blinded to endothelin-1 results and laboratory staff were blinded to patient group assignment and sample source. Endothelin-1 plasma concentrations were determined by radioimmunoassay and data were analyzed by paired t test. No difference in endothelin-1 concentration was noted with respect to placental location, central versus peripheral, or predelivery versus postdelivery sampling procedures. Overall, patients with preeclampsia had higher plasma concentrations of endothelin-1 (mean 11.0 +/- 6.6 pg/mL) compared with normotensive patients (mean 8.4 +/- 6.7 pg/mL, P < .005). The decidual-placental interface does not appear to be the source of increased plasma endothelin-1 concentrations found in severe preeclampsia. The origin of this increase remains uncertain.

Prognostic value of plasma endothelin-1 in patients with chronic heart failure

Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28 +/- 11%, in New York Heart Association (NYHA) functional class I:21, class II 35, class III: 61, class IV: 3). During a median follow-up of 361 +/- 338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested (P = 0.0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality (P = 0.00008), but only endothelin-1 remained significantly associated with outcome (P = 0.02). Patients with plasma endothelin-1 > or = 5 pg. ml-1 had a higher mortality rate than those with endothelin-1 < 5 pg. ml-1 (21% vs 4%, P = 0.001). Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.

Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms.

Some patients with angina pectoris and normal coronary arteriograms have reduced coronary flow reserve and abnormal endothelium dependent vasodilator responses. Endothelin-1 (ET-1), a potent vasoconstrictor, is an important modulator of microvascular function and may also have algogenic properties. Plasma ET-1 was measured in peripheral venous blood in 40 patients (30 women) (mean (SD) age 56 (8) years) with angina and normal coronary arteriograms and 21 normal controls (17 women) (mean (SD) age 53 (7) years). Patients with systemic hypertension, left ventricular hypertrophy, or coronary spasm were excluded. Plasma ET-1 was measured using radioimmunoassay. Thirty five patients had > or = 1 mm ST segment depression during exercise. Left bundle branch block was present in four patients at rest and in one during exercise. Mean (SD) (range) concentration of ET-1 (pg/ml) was higher in patients than in controls (3.84 (1.25) (1.97-7.42) v 2.88 (0.71) (1.57-4.48) P < 0.0001). In patients with "high" (> control mean (one SD)) ET-1 concentrations (n = 23), the time to onset of chest pain during exercise was significantly shorter (6.21 (3.9) v 9.03 (3.9) min; p = 0.01) than in patients with "low" ET-1 concentrations. Of the five patients with left bundle branch block, four had plasma ET-1 concentration > 4.0 pg/ml. Plasma endothelin is raised in patients with angina and normal coronary arteriograms and is consistent with the demonstration of endothelial dysfunction in such patients. The association between "high" plasma ET-1 and an earlier onset of chest pain during exercise suggests that endothelin may also have a role in the genesis of chest pain in patients with normal coronary arteries.

Plasma endothelin-1 in patients with left-to-right shunt

Endothelin-1 (ET-1) has been implicated in the pathogenesis of pulmonary vascular disease in patients with congenital heart disease. We studied the effect of pulmonary blood flow on plasma ET-1 concentrations. Systemic venous, pulmonary arterial, and pulmonary venous blood samples were obtained from 40 patients with atrial septal defect II ( n = 21), ventricular septal defect ( n = 10), persistent ductus arteriosus ( n = 6), and complete ( n = 2) and partial ( n = 1) atrioventricular canal at cardiac catheterization and analyzed by radioimmunoassay. Median age (range) was 5.2 years (8 months to 66 years), and the resistance ratio ( Rp Rs ) was 0.08 (0.03 to 0.67). Pulmonary vein to pulmonary artery ET-1 ratio in patients with “high flow” ( n = 26, Qp Qs ≥ 1.5 ; ET-1 ratio = 0.8) did not differ from those with “low flow” ( n = 14, Qp Qs < 1.5 ; ET-1 ratio = 1.0). We conclude that an increase in pulmonary blood flow alone does not result in an increase in plasma ET-1.

Circulating endothelin-1 concentrations in patients with chronic hypoxia.

To evaluate the behavior of plasma endothelin-1 in patients with chronic hypoxia. Fifteen male patients (mean age 52.1 +/- 3.1 years) with mild chronic obstructive pulmonary disease (COPD) were studied. Twelve healthy men (mean age 48.3 +/- 5.4 years) served as controls. Both patients and controls underwent standard pulmonary function tests, echocardiographic evaluation, and arterial blood gas evaluation. Blood samples for endothelin-1 assay were taken from a previously incannulated antecubital vein after 60 minutes of rest in the supine position. Endothelin-1 was measured by radioimmunoassay after extraction from plasma. Patients with chronic hypoxia had lower PaO2 values (66.1 +/- 6.2 mmHg) than controls (83.8 +/- 2.7 mmHg) but PaCO2 values were similar (38.1 +/- 2.5 v 36.7 +/- 3.1 mmHg, respectively). Arterial pulmonary pressure, therefore, was higher in patients (18.1 +/- 3.7 mmHg) than in controls (10.4 +/- 2.7 mmHg) as were circulating endothelin-1 concentrations (1.22 +/- 0.36 v 0.57 +/- 0.1 pg/ml). Furthermore, plasma endothelin-1 concentrations were negatively correlated with PaO2 and directly correlated with pulmonary pressure levels. No significant correlations were found in controls. These results show a clear relation between chronic hypoxia and circulating endothelin-1 concentrations. Therefore, chronic hypoxia may be regarded as an important stimulus for endothelin-1 release and as one of the main contributors to increased vasoconstriction in the vascular pulmonary bed which often accompanies lung disease.

Clinical significance of plasma endothelin-1 in patients with chronic liver disease

To determine the clinical significance of plasma endothelin-1 in chronic liver disease, these levels were measured by radioimmunoassay. The plasma endothelin-1 levels in patients with cirrhosis (N = 16) (2.04 +/- 0.25 pg/ml) and patients with hepatocellular carcinoma (N = 22) (2.23 +/- 0.17 pg/ml) increased significantly compared with controls (N = 16) (1.17 +/- 0.17 pg/ml) and patients with chronic hepatitis (N = 11) (1.09 +/- 0.19 pg/ml) (P < 0.01). The presence of ascites rather than tumor volume was associated with a significant elevation of endothelin-1. Endothelin-1 showed significant negative correlations with parameters of hepatic function, including indocyanine green clearance, serum albumin, and prothrombin time. Although endothelin-1 was not correlated with plasma renin activity and plasma endotoxin, it demonstrated a significant positive correlation with the plasma level of atrial natriuretic peptide (r = 0.42, P < 0.01). These findings demonstrate that plasma endothelin-1 increased in proportion to the severity of liver damage and may be causally related with the derangement of systemic/renal hemodynamics and fluid and electrolyte homeostasis seen in advanced liver disease.

Neurohumoral effects of ramipril in angina pectoris: A double-blind, placebo-controlled trial against isosorbide dinitrate and the combination of ramipril plus isosorbide dinitrate

Elevated levels of neurohormones are directly correlated with cardiovascular risk. This double-blind, parallel-group study was designed to examine whether treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril, could positively influence the plasma levels of neurohormones—plasma renin activity (PRA), aldosterone, atrial natriuretic peptide (ANP), and endothelin—and whether differences exist between treatments with ramipril, isosorbide dinitrate (ISDN) alone, ramipril + ISDN or placebo. Thirty-two patients (1 woman, 31 men) with congestive heart failure, aged 42 to 72 years (mean, 62.8 years), were enrolled in four parallel study groups. Test medications were administered as a single dose in a double-blind, parallel-group manner with a double-dummy technique as follows: ramipril (5 mg), ISDN (20 mg), the combination ramipril + ISDN, and placebo. PRA, aldosterone, ANP, and endothelin concentrations were estimated before and 1, 2, 3, 4, 6, 8, and 24 hours after drug administration. Plasma endothelin levels decreased significantly in the groups receiving ramipril treatment, whereas no change was seen after placebo or ISDN administration. No significant changes were seen for ANP, whereas PRA increased and aldosterone decreased in the groups receiving ramipril. A single dose of ramipril reduced plasma endothelin in patients with angina pectoris, whereas no significant changes were observed for ANP. The changes seen with PRA and aldosterone were as expected for ACE inhibitors.

Increased plasma endothelin-1 in the early hours of acute myocardial infarction

Endothelin is a novel endothelium-derived vasoactive peptide with potent vasoconstrictor action in the coronary bed; however, its possible contribution to myocardial ischemia and infarction is not known. Plasma endothelin-1 concentration was measured with use of a radioimmunoassay in serial venous samples from 22 patients over a 72 h period after acute myocardial infarction (14 patients with uncomplicated infarction [group I] and 8 patients with hemodynamic or ischemic sequelae [group II]). Twenty-two normal subjects and seven patients with stable angina served as the control subjects. Endothelin-1 levels in patients with stable coronary disease were not different from those of normal subjects (0.62 +/- 0.56 and 0.76 +/- 0.38 pg/ml, respectively). In group I, plasma levels of endothelin-1 rose sharply after myocardial infarction, reaching a peak of 4.95 +/- 0.78 pg/ml at 6 h after the onset of chest pain (p less than 0.05 compared with values in control subjects) and returning rapidly toward the normal range by 24 h. Patients with complicated infarction (group II) demonstrated a similar rapid increase in plasma endothelin-1 to a peak value of 8.29 +/- 1.95 pg/ml; however, plasma endothelin-1 remained elevated in these patients, becoming significantly different from values in group I at 48 and 72 h. There was no correlation between peak increases in creatine kinase and peak endothelin-1 in either group, suggesting that the stimulus for elevation of endothelin-1 was not myocardial necrosis itself. Furthermore, left ventricular ejection fraction did not correlate with the increase in endothelin-1 in group I patients, whereas there was a significant inverse relation between ventricular function and plasma endothelin-1 in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Release of endothelin from cultured bovine endothelial cells

Recently discovered endothelin is a powerful vasoconstrictor of vascular smooth muscle in vitro, which also profoundly affects the mechanical function of the heart [ 1, 2]. An increased level of plasma endothelin in patients with acute myocardial infarction suggests the enhanced release of endothelin from vascular endothelium under pathophysiological conditions of the heart [ 3]. The reperfusion of ischemic myocardium is associated with the activation of polymorphonuclear leukocytes (PMN) generating oxygen-derived free radicals (OFR), as well as, enhanced responsiveness of myocardial α 1-adrenergic receptors [ 4,5]. Both OFR and catecholamines are implicated in the modulation of release of endothelium-derived peptides [ 6].

Elevated plasma endothelin in patients with diabetes mellitus

Plasma concentrations of endothelin, a vasoconstrictor peptide released from vascular endothelial cells, have been measured by radioimmunoassay in 100 patients with diabetes mellitus and 19 healthy subjects. The plasma immunoreactive-endothelin concentrations were found to be greatly raised in the patients with diabetes (1,880 +/- 120 fmol/l, mean +/- SEM) compared with the healthy subjects (540 +/- 50 fmol/l, p less than 0.005). The elevation of immunoreactive-endothelin could not be explained by secondary changes in blood pressure or renal disease and did not correlate with the presence of diabetic retinopathy, duration of diabetes mellitus, fasting blood glucose or serum fructosamine. Fast protein liquid chromatographic analysis of the diabetic plasma immunoreactive-endothelin showed three forms, one in a very big molecular weight position, one intermediate and one in the position of endothelin-1 itself. No material appeared in the positions of endothelin-2 and 3. Chromatographic analysis of normal plasma showed only the big molecular weight peak while material in the endothelin-1, 2 or 3 positions was below detection. The elevation of endothelin in diabetic patients may be a marker of, and further exacerbate, their vascular disease.