Plasma endothelin in chronic heart failure.

BACKGROUND. Endothelins are recently characterized vasoconstrictor peptides. As chronic heart failure (CHF) is characterized by peripheral arteriolar and renal vasoconstriction, we have measured venous plasma endothelin-like immunoreactivity ("endothelin") in patients with this syndrome. METHODS AND RESULTS. Compared with age- and sex-matched healthy volunteers (mean +/- SEM plasma endothelin concentration 6.4 +/- 0.3 pmol/l, n = 16), patients with severe CHF had elevated peripheral venous endothelin concentrations (12.4 +/- 0.6 pmol/l, n = 47, p less than 0.01). Plasma endothelin did not increase with exercise in normal subjects or in patients. Plasma endothelin concentration (mean, 13.4 +/- 0.9 pmol/l) did not correlate with plasma atrial natriuretic factor concentration (mean, 88.9 +/- 11.9 pg/ml) in patients with CHF (n = 21). There was also no correlation between plasma endothelin and serum urea or between endothelin and serum creatinine in patients with CHF (n = 34). There was, however, significant renal extraction of endothelin (aorta, 11.1 +/- 0.8 pmol/l; renal vein, 8.8 +/- 0.6 pmol/ml; p = 0.02) in patients with CHF (n = 13). CONCLUSIONS. Evidence suggests that circulatory endothelin concentrations in the range 5-40 pmol/l are vasoactive. Consequently, the endothelin concentrations found in patients with CHF may be of pathophysiological significance.     

Plasma LRH levels in chronic renal failure before and during haemodialysis

Endogenous immunoreactive luteinizing hormone - releasing hormone (LRH) in plasma was determined in 6 male and 7 female patients with chronic renal failure before and during haemodialysis. Basal plasma LRH levels ranged from 5.8 to 23.0 pg/ml and, in 11 out of 13 patients, were above the levels seen in healthy subjects (less than 7 pg/ml for men and less than 8 pg/ml for women). This immunoreactivity was eluted iun identical fractions with synthetic LRH and plasma extracts from climacteric women on Sephadex G-25 chromatography, and the dilution gave a displacement curve parallel to the standard. Within 5 h of haemodialysis, these high LRH levels declined into the normal range. The concentrations of LH in plasma in these patients were also elevated, but those of testosterone in male patients were decreased. These results suggest 1) that elevated plasma LRH reflects decreased feedback inhibition by primary gonadal failure and might in turn be responsible at least in part for high concentrations of plasma LH in chronic renal failure, and 2) that plasma LRH is mainly not bound to plasma proteins.     

Plasma levels of atrial natriuretic peptide in patients with chronic renal failure

Plasma levels of atrial natriuretic peptide (ANP) were measured in 57 patients with chronic renal failure (CRF) using a specific and sensitive RIA. The mean plasma ANP level in CRF patients [173 +/- 17.0 pg/ml (+/- SEM); n = 57] was significantly higher than that in normal subjects (37.6 +/- 1.9 pg/ml; n = 40). No significant correlation was found between plasma ANP and serum creatinine concentrations. CRF patients treated by maintenance hemodialysis had significantly higher plasma ANP levels than did nondialysis patients. Hemodialysis significantly decreased plasma ANP, and changes in plasma ANP levels after hemodialysis differed from those in serum creatinine concentrations. The mean serum creatinine concentration rose significantly 24 h after hemodialysis. In contrast, plasma ANP levels did not change in the first 24 h, but then rapidly increased. When ANP in predialysis plasma from patients with CRF was analyzed by reverse phase high performance liquid chromatography, the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results suggest that expanded extracellular volume stimulates the secretion of ANP in CRF patients and that this increase in ANP release reflects a mechanism of compensation in volume homeostasis in man.     

Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure.

BACKGROUND. Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. METHODS AND RESULTS. We tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14 +/- 0.45 l/m/m2, and pulmonary wedge pressure was increased to 22 +/- 7 mm Hg. The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61 mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07 +/- 4.13 pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals (3.7 +/- 0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically significant (p less than 0.0001). Endothelin-1 significantly correlated with pulmonary pressures (systolic, r = 0.78; mean, r = 0.80; diastolic, r = 0.77; all p less than 0.003) and pulmonary vascular resistance (r = 0.65, p less than 0.01). Endothelin-1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r = 0.88, p less than 0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. CONCLUSIONS. Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation.     

Plasma immunoreactive endothelin in essential hypertension

PURPOSE: Endothelin plays a role in the regulation of vascular tonus. Therefore, it has been hypothesized that increased production or release of endothelin or both may contribute to the pathogenesis of hypertension. To assess any changes in the plasma endothelin concentration in essential hypertension, plasma immunoreactive endothelin concentrations were measured in patients with essential hypertension. PATIENTS AND METHODS: We measured plasma immunoreactive endothelin concentrations in 42 subjects with essential hypertension, 12 subjects with borderline hypertension, and 25 normotensive control subjects. RESULTS: The concentrations were higher in hypertensive patients than in borderline hypertensive patients and normotensive subjects (both p less than 0.05), although values in normotensives and hypertensives overlapped. Reverse-phase high-performance liquid chromatography (HPLC) and radioimmuno-assay showed two components of plasma endothelin, one corresponding to synthetic endothelin-1 (1-21) and the other corresponding to synthetic big endothelin (human, 1-38). The HPLC profile of plasma endothelin of hypertensive patients was the same as that of normotensive subjects. Hypertensives with reduced glomerular filtration rates or increased serum creatinine levels had higher plasma endothelin concentrations than hypertensive patients as a whole (p less than 0.05). Mean blood pressure and serum creatinine levels were correlated to plasma endothelin in the hypertensives. Correlation was negative between glomerular filtration rate and the endothelin level in the hypertensives. CONCLUSION: Plasma endothelin was elevated in many hypertensive patients with severe hypertension or renal involvement. Its major components were endothelin-1 and big endothelin.     

Pulmonary hypertension in patients with chronic renal failure

BACKGROUND: Many etiologies causing pulmonary hypertension (PH) have been reported, and one of the background disease seen with patients with PH is chronic renal failure (CRF); however, the pathogenesis of PH in this group of patients is not explained satisfactorily. OBJECTIVES: The aims of this study were to evaluate the incidence of unexplained PH among patients with CRF and to suggest possible etiologic factors. METHODS: Two hundred and eleven patients with CRF were evaluated and the ones who have comorbid conditions that cause PH were excluded. Pulmonary arterial pressure (PAP) and cardiac functions were evaluated by Doppler echocardiography. Arteriovenous fistula (AVF) flow was measured by Doppler sonography. The patients were followed for at least 6 months. RESULTS: Forty-eight CRF patients (20 males, 28 females) were included: 23 were predialysis patients, and 25 patients received hemodialysis via AVF. Patients were followed for 7.5 +/- 1.01 months. Systolic PAP >35 mm Hg was found in 56% (14/25) of patients receiving hemodialysis (36.8 +/- 10.7 mm Hg) and in 39.1% (9/23) of predialysis patients (29.5 +/- 9.5 mm Hg). The parathyroid hormone level, cardiac output values and CRF duration were found to be increased in patients with elevated systolic PAP (p < 0.05). AVF flow and AVF duration were positively correlated with systolic PAP in patients receiving hemodialysis (p < 0.05). There was a negative correlation between systolic PAP and residual urine volume (p < 0.05). AVF compression in hemodialysis patients decreased systolic PAP from 36.8 +/- 10.7 to 32.8 +/- 10.5 mm Hg. Systolic PAP values were increased at the end of the study in the predialysis group, whereas they were decreased at the end of the follow-up in the hemodialysis group (36.9 +/- 10.5 and 32.04 +/- 10.5 mm Hg, respectively). CONCLUSIONS: This study demonstrates a high incidence of PH among patients with CRF. CRF duration, AVF flow, parathyroid hormone level and cardiac output may be involved in the pathogenesis of PH. The effective hemodialysis and dry weight reduction decreased systolic PAP values.     

Plasma norepinephrine and dopamine-beta-hydroxylase activity in chronic renal failure.

To evaluate the activity of the sympathetic nervous system in chronic renal failure, plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) activity were measured by a radioenzymatic assay and a photometric assay respectively. The level of plasma NE was significantly higher in 14 patients with hemodialysis than in healthy individuals (p less than 0.001). The level of plasma NE fell significantly in 6 patients with hemodialysis receiving 0.30-0.45 mg/day of clonidine hydrochloride (a depressor of the sympathetic outflow from the central nervous system) (p less than 0.05). Systolic blood pressure was correlated with the level of plasma NE in patients with hemodialysis who were not receiving clonidine. They had high level of plasma NE and low level of plasma DBH activity. Therefore, this findings suggest that high level of plasma NE in chronic renal failure is caused not only by decreased urinary excretion, but also by increased overflow from the sympathetic nervous clefts.     

Plasma myeloperoxidase levels in patients with chronic heart failure

Increased oxidative stress and endothelial dysfunction are commonly observed in patients with chronic heart failure (HF). The relation between myeloperoxidase (MPO), an inflammatory marker with mechanistic links to plaque vulnerability and abnormal ventricular remodeling, and degrees of severity in chronic HF has not been reported. Plasma MPO levels were measured in 105 normal controls (no history of HF or left ventricular dysfunction) and 102 patients with chronic systolic HF (left ventricular ejection fraction <50%), and the relations among plasma MPO levels, plasma B-type natriuretic peptide levels, and the left ventricular ejection fraction were examined. Plasma MPO levels in patients with chronic systolic HF were significantly elevated compared with those of healthy controls (1,158 +/- 2,965 vs 204 +/- 139 pM, p <0.0001). Plasma MPO levels increased in parallel with increasing New York Heart Association class (p <0.0001) and were correlated with plasma B-type natriuretic peptide levels (Spearman's r = 0.39, p <0.0001). Levels of MPO were strongly associated with the prevalence of HF (unadjusted odds ratio 30.3, 95% confidence interval 11.1 to 94.5) and remained significant when adjusted for age and B-type natriuretic peptide (odds ratio 27.7, 95% confidence interval 3.6 to 371.1). In conclusion, in a cohort of patients with chronic HF, plasma MPO levels were elevated compared with those of normal controls and were associated with worsening functional class.     

慢性心力衰竭患者血浆血管抑制因子2的研究

目的研究慢性心力衰竭(CHF)患者血浆血管抑制因子2(VS2)水平及其潜在临床意义。方法参照Framingham临床心力衰竭的诊断标准,入选216例CHF患者为研究组,其中无或轻度CHF症状93例,中重度CHF症状123例;缺血性心脏病99例,非缺血性心脏病117例。选择同期171例体检健康者为对照组。用ELISA法测定血浆VS2水平。结果研究组血浆VS2水平显著低于对照组[0.805(0.547,1.187)μg/L vs 0.983(0.510,1.783)μg/L,P=0.011]。无或轻度CHF症状与中重度CHF症状者VS2水平比较无显著差异(P=0.908),缺血性心脏病与非缺血性心脏病患者VS2水平比较无显著差异(P=0.409)。123例中重度CHF症状患者VS2水平与心率呈负相关(r=-0.198,P=0.028)。结论 CHF患者血浆VS2水平降低,VS2与心力衰竭程度无关。     

Plasma endothelin levels in cirrhotic subjects.

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.     

Big endothelin and chronic heart failure

In a group of 124 patients the authors investigated the importance of assessment of plasma levels of big endothelin and endothelin 1 in patients with chronic heart failure as compared with other currently used non-invasive parameters. A six fold increase of plasma levels of both substances was found in patients in functional class NYHA IV as compared with patients in class NYHA II-III. But even patients in the milder stage of NYHA had twice as high values as compared with the standard of the healthy population. Similarly patients with interstitial pulmonary oedema had a twice as high level of both parameters as compared with patients who had a normal finding on X-ray or merely a redistribution of the pulmonary vascularization. The sensitivity of assessment of plasma levels is such that this examination could become part of the basic diagnosis.     

Serum dopamine-beta-hydroxylase activity in essential hypertension and in chronic renal failure with hypertension.

Elevated serum DBH (dopamine-beta-hydroxylase) activity was found in essential hypertension. The elevated level was not reduced when blood pressure was brought to normotensive level by administration of thiazide or rauwolfia. In contrast, serum DBH activity was low in both normotensive and hypertensive patients treated on prolonged hemodialysis. However, there was no correlation between serum DBH activity and blood pressure level. It was suggested that the pathogenesis of high blood pressure might be different between essential hypertension and hypertension with chronic renal failure, and that measurement of serum DBH activity might help for clinical differentiation of essential hypertension from certain forms of secondary hypertension.     

Plasma endothelin is increased in early essential hypertension

Local vascular generation of endothelin-1 (ET-1) may contribute to elevated peripheral resistance in hypertension. We tested the hypothesis that immunoreactive ET production in the forearm circulation is increased in early essential hypertensive subjects. Ten young, previously untreated male patients with mild essential hypertension and no signs of target organ damage were compared with matched normotensive subjects in an outpatient setting. Arterial and venous samples were obtained from indwelling catheters in the brachial artery and the medial cubital vein, respectively. Samples were collected at baseline and after induction of endothelium-dependent (acetylcholine) vasodilation. Immunoreactive ET (ET) was measured after column extraction by a sensitive radioimmunoassay employing a C-terminal ET-1 antibody with negligible cross-reaction to big-ET. Individual recovery rates were determined for each sample.Basal ET was significantly higher in hypertensive than in normotensive subjects, both in venous and arterial samples (P < .01). This difference was also present after correction for recovery (P < .01). There was no significant difference between venous and arterial ET concentrations. Local vasodilation did not change arterial or venous ET levels. In conclusion, plasma ET is increased in young, untreated, essential hypertensive subjects with no signs of target organ damage. The increased circulating immunoreactive ET may point to a role for the peptide early in the development of high blood pressure.     

Vitamin levels in chronic renal failure and need for supplementation

Deficiencies of water-soluble vitamins may occur in uremic patients mainly because of restricted consumption and of loss during chronic hemo- and peritoneal dialysis. Although the daily requirement for most vitamins is not well defined in chronic renal failure supplementation of the vitamins thiamine, riboflavin, pyridoxine, pantothenic acid, niacin and ascorbic acid, the form of one multivitamin preparation without vitamin A as well as folic acid in dialysis patients after each dialysis is recommended. There is no need for vitamin B12, vitamin A and vitamin E.