atrial-natriuretic-factor and Uremia

Patients with end-stage renal disease have a deranged sodium and water homeostasis leading to chronic volume overload. Atrial natriuretic peptides (ANPs) are circulating hormones that are involved in the regulation of volume homeostasis, blood pressure control, and electrolyte balance. In hemodialysis patients plasma ANPs are highly elevated and decrease during the dialysis session when fluid is removed. However, hemodialysis treatment never corrects the defect in the metabolism of these peptides and their circulating concentrations do not return to levels found in healthy controls. Besides uremia and chronic volume overload, other factors such as cardiac dysfunction or hypertension may contribute to the elevated plasma concentrations of ANPs. ProANP fragments which derive from the N-terminus of the ANP prohormone have been also found in the circulation and they have biological functions similar to alpha-ANP (ie, the C-terminus of the prohormone). The proANP peptides proANP(1-30), proANP(31-67), and proANP(1-98) are increased in patients undergoing regular hemodialysis treatment, but their decrease during the dialysis procedure is less pronounced than for alpha-ANP or cyclic GMP. Cellulose triacetate dialyzer membrane material lowered the plasma concentrations of proANP(1-30), proANP(31-67), and proANP(1-98) significantly more than polysulfone, whereas alpha-ANP and cyclic GMP were not differently affected. Aside from a variety of factors that influence circulating natriuretic factors in the uremic patient, there is evidence for differences in dialyzer membrane adsorption of these peptides which speculatively may be linked to dialysis-associated symptoms.

Topics: Adsorption; Atrial Natriuretic Factor; Humans; Kidney; Kidney Failure, Chronic; Plasma Volume; Renal Dialysis; Uremia

A new appreciation of the hemodynamic, hormonal, and neural derangements associated with unexplained renal failure in patients with severe liver disease has led to a reappraisal of the limited therapeutic approaches to the hepatorenal syndrome. Although the prognosis generally remains dismal, specific supportive measures are now available for the management of selected patients.

Topics: Atrial Natriuretic Factor; Diagnosis, Differential; Hemodynamics; Hepatorenal Syndrome; Humans; Immersion; Kidney Diseases; Liver Cirrhosis; Prognosis; Renal Circulation; Sympathetic Nervous System; Uremia

Short daily hemodialysis (HD) has a protective effect against dialysis-induced hypotension (DIH). We examined whether this effect extends beyond the treatment period.. We analyzed clinical variables in 6 patients (5 with diabetes mellitus) who underwent conventional hemodialysis (CHD) for 4 h three times weekly for 12 weeks; then short daily HD for 2 h six times weekly for 12 weeks, and then 12 more weeks of CHD. All patients had been given vasopressors for severe DIH.. The severe DIH disappeared during the short daily HD. There were significant decreases in body weight (BW), cardiothoracic ratio (CTR), blood pressure (BP), normal saline solution (NSS) amount (62.8 +/- 26.4 vs. 9.8 +/- 7.4 ml/session, p < 0.05), frequency (0.60 +/- 0.26 vs. 0.10 +/- 0.07 infusions/session, p < 0.05) and postdialysis atrial natriuretic peptide (ANP) (176.8 +/- 56.4 vs. 104.8 +/- 42.3 pg/ml, p < 0.05). Weekly ultrafiltration volume (6.3 +/- 0.9 vs. 7.9 +/- 0.7 l, p < 0.05) was significantly higher during the short daily HD period than during the first CHD period. The vasopressor treatment was therefore stopped or reduced in all patients during the short daily HD period. Because DIH recurred in the second CHD period despite a significant increase in BP, the vasopressor treatment was resumed in 5 patients. BW, CTR, NSS infusion amount and frequency, or postdialysis ANP did not differ significantly between the short daily HD and second CHD periods.. The protective effect of short daily HD against DIH lasted more than 12 weeks after the treatment ended. We therefore conclude that temporary short daily HD is useful for preventing DIH.

Topics: Aged; Anemia; Antihypertensive Agents; Appointments and Schedules; Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Diabetic Nephropathies; Echocardiography; Erythropoietin; Female; Ferritins; Humans; Hypertension, Renal; Hypotension; Iron; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Recombinant Proteins; Renal Dialysis; Uremia

Angiotensin-converting enzyme (ACE) inhibitors ameliorate the progression of renal disease. In combination with vitamin D receptor activators, they provide additional benefits. In the present study, uremic (U) rats were treated as follows: U+vehicle (UC), U+enalapril (UE; 25 mg/l in drinking water), U+paricalcitol (UP; 0.8 μg/kg ip, 3 × wk), or U+enalapril+paricalcitol (UEP). Despite hypertension in UP rats, proteinuria decreased by 32% vs. UC rats. Enalapril alone, or in combination with paricalcitol, further decreased proteinuria (≈70%). Glomerulosclerosis and interstitial infiltration increased in UC rats. Paricalcitol and enalapril inhibited this. The increase in cardiac atrial natriuretic peptide (ANP) seen in UC rats was significantly decreased by paricalcitol. Enalapril produced a more dramatic reduction in ANP. Renal oxidative stress plays a critical role in inflammation and progression of sclerosis. The marked increase in p22(phox), a subunit of NADPH oxidase, and decrease in endothelial nitric oxide synthase were inhibited in all treated groups. Cotreatment with both compounds inhibited the uremia-induced increase in proinflammatory inducible nitric oxide synthase (iNOS) and glutathione peroxidase activity better than either compound alone. Glutathione reductase was also increased in UE and UP rats vs. UC. Kidney 4-hydroxynonenal was significantly increased in the UC group compared with the normal group. Combined treatment with both compounds significantly blunted this increase, P < 0.05, while either compound alone had no effect. Additionally, the expression of Mn-SOD was increased and CuZn-SOD decreased by uremia. This was ameliorated in all treatment groups. Cotreatment with enalapril and paricalcitol had an additive effect in increasing CuZn-SOD expression. In conclusion, like enalapril, paricalcitol alone can improve proteinuria, glomerulosclerosis, and interstitial infiltration and reduce renal oxidative stress. The effects of paricalcitol may be amplified when an ACE inhibitor is added since cotreatment with both compounds seems to have an additive effect on ameliorating uremia-induced changes in iNOS and CuZn-SOD expression, peroxidase activity, and renal histomorphometry.

Topics: Aldehydes; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Enalapril; Ergocalciferols; Female; Glomerulonephritis; Kidney; NADPH Oxidases; Nitric Oxide Synthase Type II; Oxidative Stress; Proteinuria; Rats; Receptors, Calcitriol; Superoxide Dismutase; Uremia

The diagnostic value of natriuretic peptides in uremic cardiomyopathy has not been defined, nor has the effect of a hemodialysis (HD) session on peptides.. We performed an observational study of 100 white adult outpatients in New York Heart Association class I-II, with neither diabetes nor ischemic heart disease, 50 of whom had idiopathic dilated cardiomyopathy (DCM) and 50 of whom had uremic cardiomyopathy and were undergoing HD. We measured plasma N-terminal proB-type natriuretic peptide (NT-proBNP), BNP, and atrial natriuretic peptide (ANP) both before and after a dialysis session. Doppler echocardiograms were evaluated. We performed multiple regression analysis on the logarithm of peptide concentrations using clinical, laboratory, and echocardio-Doppler data as explanatory variables.. Mean peptide concentrations were higher in the HD group, with an HD:DCM ratio of 25 for NT-proBNP and 5 for BNP and ANP. Peptides were correlated with each other (r > 0.85). After HD, NT-proBNP significantly increased by 14%, BNP decreased by 17%, and ANP decreased by 56%. Predialysis concentrations correlated with postdialysis values (r > 0.85). A multiple regression equation significantly fitted the observed peptide concentrations, both pre- and postdialysis, using the same set of 4 variables: disease group (DCM or HD), diastolic pattern, left atrial volume, and body mass index.. Renal dysfunction was a confounder for natriuretic peptides, which were present in higher concentrations in the uremic patients with milder cardiac dysfunction than in those with idiopathic DCM without renal dysfunction. Left diastolic function pattern and atrial volume were cardiac determinants of peptide concentrations in DCM and HD.

Topics: Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Heart; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Renal Dialysis; Uremia

Hypertension and anemia may be causes of left ventricular hypertrophy (LVH) in uremia but the molecular mechanism is not known. Uremia was induced in male Spraugue Dawley rats by 5/6 nephrectomy. The following groups of rats were studied for 6 weeks; uremic rats (U) fed ad. lib., control rats (C) pair-fed with U, U rats given hydralazine (100 mg/kg/day) (UH), U rats given erythropoietin (48 U/kg/week, i.p.) (UE). Both diastolic and mean arterial pressures are higher (P < 0.01) in U and UE compared with C whereas both pressures in UH were normalized. Hemoglobin in U was lower than in C, and was normalized in UE. U, UH and UE had higher heart weight/body weight ratios (HW/BW) as well as left ventricular weight/body weight ratios (LV/BW) compared with C (P < 0.01). Compared with U, UH has lower HW/BW and LV/BW (P < 0.05) and UE has normal HW/BW but lower LV/BW than U (P < 0.05). To see if the gene expression in uremic LVH is similar to that described in pressure overload LVH in which mRNA levels of angiotensin converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), atrial natriuretic factors (ANF) and skeletal a- actin were increased, we measured these mRNA levels by Northern analysis. TGF-beta1, ACE and alpha-actin mRNA levels were not changed in all 4 groups. ANF mRNA in U and UE was increased 3 fold over C, and normalized in UH. Treatment of anemia with erythropoietin improved uremic LVH but did not change ANF mRNA; whereas treatment of hypertension with hydralazine normalized ANF mRNA but did not completely correct uremic LVH. Thus, gene expression in uremic LVH is distinct from that in pressure-overload LVH, suggesting that other unidentified factor(s) might be involved in uremic LVH.

Topics: Actins; Anemia; Animals; Atrial Natriuretic Factor; Erythropoietin; Gene Expression; Heart Ventricles; Hydralazine; Hypertension; Hypertrophy, Left Ventricular; Male; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1; Uremia

Ultrafiltration during haemodialysis (HD) may be the cause of blood pressure (BP) decline due to reduction of blood volume. In some patients, however, BP does not decrease or even rises during HD. The aim of the study was to answer the question: do uraemic hypertensive patients, showing a decline of mean blood pressure (MAP) during HD session (group A) differ from those showing a stable MAP during HD session (group B) with respect to hormonal profile of aldosterone (ALD), vasopressin (AVP), atrial natriuretic peptide (ANP), endothelin-1,2 (ET-1,2), blood nitric oxide (NO) and plasma renin activity (PRA). A total of 39 haemodialysed, hypertensive patients (17 female, 22 men) were studied. 24 patients (group A) showed a MAP decline of 10 mm Hg or more, while 15 patients (group B) showed MAP changes of less than +/- 10 mm Hg during HD session. PRA, ALD, AVP, ANP, ET-1,2, NO concentration were assessed in blood samples withdrawn from the arterial blood line before HD and after 60, 120, 180 and 240 minutes of HD session. Plasma ET-1,2 and blood NO concentration were also assessed after 30 minutes of HD. BV was continuously monitored with a Crit-Line equipment, BP was measured before and every 30 minutes on HD. Before HD session both examined groups showed similar baseline plasma levels of ALD, AVP, ANP, ET-1,2, NO, PRA and MAP. A 4-hours HD induced a significant increase in plasma ALD and AVP concentrations and a significant decline in ANP level in both groups of patients. In group A, PRA and blood NO concentration increased significantly, while plasma ET-1,2, level did not change during HD. In group B, no significant changes in PRA and blood NO level were noticed, while plasma ET-1,2 rose markedly. In addition in group B, a significant positive correlation was found between MAP and plasma ET-1,2 level changes, but a significant negative correlation between MAP and blood NO level changes.. Patients with a decline of MAP over 10 mm Hg during HD differ from those with a stable MAP by a different response of plasma ET and blood NO to HD induced volume changes.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Volume; Female; Humans; Hypertension; Male; Nitric Oxide; Renal Dialysis; Severity of Illness Index; Uremia; Vasopressins

We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia.. Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured.. The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P < 0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P < 0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P < 0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P < 0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P < 0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r = -0.59, P < 0.01) and plasma AII levels (r = -0.80, P < 0.01).. Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.

Topics: Adult; Aged; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Catecholamines; Chronic Disease; Female; Humans; Hypotension; Male; Middle Aged; Parathyroid Hormone; Renin; Uremia

To determine the role of vasoactive peptides such as endothelin (ET), calcitonin gene-related peptide (CGRP) and human atrial natriuretic peptide (hANP) in the regulation of blood pressure in uremic patients, and to determine the effect of various types of dialyzer membranes on hemodialysis (HD)-induced changes in plasma levels of such peptides, plasma ET, CGRP and hANP were measured in HD patients and patients on continuous ambulatory peritoneal dialysis (CAPD). Plasma levels of ET, CGRP, and hANP were significantly higher in HD and CAPD patients than in healthy subjects. There were no significant differences in plasma levels of ET, CGRP, and hANP between hypertensive and normotensive HD patients, and no significant correlation was observed between HD-induced changes in plasma levels and changes in blood pressure. Plasma levels of ET decreased when HD was performed using high-flux membranes, such as polyacrylonitrile (PAN), polymethyl methacrylate (PMMA) and cellulose triacetate (CTA), but did not decrease using a saponified cellulose (SC) membrane. Plasma levels of CGRP decreased in the case of PAN, but increased significantly with PMMA and showed no change with SC and CTA. Plasma levels of hANP decreased in all types of dialyzer membranes due to decreased secretion. These results indicate that the effect of HD on plasma levels of ET and CGRP, but not hANP, depends on the type of dialyzer membrane used.

Topics: Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Endothelins; Female; Humans; Hypotension; Kidneys, Artificial; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Uremia

Topics: Aged; Atrial Natriuretic Factor; Dialysis Solutions; Female; Humans; Infusions, Parenteral; Male; Peritoneal Dialysis, Continuous Ambulatory; Uremia

In order to evaluate the hormonal regulation of blood pressure (BP) in uraemia 12 patients on chronic maintenance dialysis and 14 healthy controls were studied. BP and plasma concentrations of atrial natriuretic peptide (ANP), cyclic 3',5'-guanosine monophosphate (cGMP), and intact parathyroid hormone (PTH(1-84)) were determined before, during, and after a 60 min noradrenaline infusion 0.1 micrograms kg-1 body wt. min-1. Mean BP increased to the same extent in the uraemic patients (median 15 mmHg, range 6-25 mmHg) as in the controls (12 mmHg, 5-25 mmHg). ANP increased during noradrenaline infusion both in patients (7.2 to 8.3 pmol/l, medians, p < 0.01) and in controls (4.4 to 6.0 pmol/l, p < 0.01), and so did cGMP (patients: 31.6 to 35.9 nmol/l, p < 0.05; controls: 6.6 to 8.7 nmol/l, p < 0.01). PTH(1-84) was higher in the uraemic patients than in the controls, but was unchanged during noradrenaline infusion in both groups. Correlation analyses gave no evidence of a direct relation between BP and ANP, but basal PTH(1-84) was negatively correlated to basal mean BP in the patients (rho = -0.615, p < 0.05), but not in the controls. In conclusion, noradrenaline induced similar elevations of BP in dialysis patients as in healthy controls despite elevated ANP and PTH(1-84) in the patients, and ANP release was stimulated in both groups. PTH(1-84) may participate in blood pressure regulation in uraemic patients.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Norepinephrine; Parathyroid Hormone; Renal Dialysis; Uremia

To evaluate the interaction between plasma levels and the systemic uptake of atrial natriuretic factor (ANF) with thyroid hormone levels during acute renal failure (ARF), seven groups of rats were analyzed: Group 1, Controls (C); Group 2, ARF; Group 3, filtering kidney with uremia; Group 4, ARF with thyroxine (T4) supplement (ARF + T4); Group 5, thyroidectomy (Tx); Group 6, ARF on Tx rats (Tx + ARF); Group 7, Tx + ARF supplemented with T4 (Tx + ARF + T4). Plasma creatinine (Cr), urea, T4, blood volume, and ANF were measured; ANF half-life (ANF t1/2; expressed in seconds) was calculated. Rats with ARF developed uremia (Cr, 377 +/- 58 versus 41 +/- 5 mumol/L), significant reduction in T4 (40 +/- 4 versus 89.2 +/- 6 nmol/L). elevation of ANF (287.7 +/- 35 versus 60.9 +/- 8 fmol/mL), and lengthening of ANF t1/2 (69.7 +/- 8 versus 37.2 +/- 6 s) compared with C (P less than 0.01). T4 supplements to ARF rats resulted in a lesser degree of uremia (Cr, 283 +/- 27; P less than 0.05) and normalization of ANF t1/2 (31.4 +/- 5); however, ANF levels remained higher than C (100.4 +/- 11.4 versus 60.9 +/- 8; P less than 0.01). Tx by itself did not change either parameter. The filtering kidney with uremia group developed mild uremia (Cr, 199 +/- 8), T4 fell (58 +/- 8), ANF levels rose (83.4 +/- 5.4), and ANF t1/2 was prolonged (54.5 +/- 12). Tx before ARF doubled the ANF level and lengthened ANF t1/2 similarly than in ARF. T4 addition (Tx + ARF + T4) normalized ANF t1/2 (29.8 +/- 3) in spite of a persistently high ANF (145.7 +/- 21). Blood volume did not change in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Biological Transport, Active; Half-Life; Male; Rats; Rats, Inbred Strains; Thyroidectomy; Thyroxine; Uremia

alpha-Human atrial natriuretic peptide (ANP) concentrations were measured in 11 diabetic patients with uremia and in 16 nondiabetic uremic controls undergoing renal transplantation after preanesthetic volume expansion with 1000 ml saline solution within 10 min. Two diabetic and seven nondiabetic patients received grafts from living donors and the rest from cadaveric donors. Volume expansion induced a significant increase in the cardiac filling pressures (P less than 0.001), which were kept at that level especially at declamping, which was preceded by mannitol infusion. The baseline mixed venous ANP levels were significantly higher in the diabetic (252 +/- 6 pg/ml) than in the nondiabetic group (103 +/- 14 pg/ml; P less than 0.05). In the nondiabetic group, ANP increased to 177 +/- 40 pg/ml as a response to volume loading (P less than 0.05); it was not clearly changed in the diabetic group. Arterial ANP increased from 267 +/- 55 to 343 +/- 75 pg/ml in the diabetic group (P less than 0.05 and from 102 +/- 17 to 147 +/- 31 pg/ml in the nondiabetic group (P less than 0.05). During transplantation, mixed venous ANP decreased to 125 +/- 55 pg/ml in the diabetic and to 80 +/- 10 pg/ml in the nondiabetic group (P less than 0.001). About 30% of circulating ANP was taken up by the transplant irrespective of postoperative graft function. Two patients in each group showed delayed diuresis requiring postoperative dialysis therapy (22% of all cadaveric transplantations). ANP levels at declamping had no correlation to the outcome of kidney function.

Topics: Adult; Atrial Natriuretic Factor; Blood Volume; Diabetic Nephropathies; Female; Humans; Kidney Transplantation; Lactates; Lactic Acid; Male; Renin; Uremia; Vasopressins

We treated a patient with refractory biventricular heart failure, dilutional hyponatremia and prerenal azotemia, by means of ultrafiltration. After ultrafiltration, gas exchange and cardiac output improved, with concomitant reduction of systemic and pulmonary vascular resistances. Despite a decrease of right atrial and wedge pressure, atrial natriuretic factor rose and plasma renin activity decreased.

Topics: Atrial Natriuretic Factor; Blood Gas Analysis; Endocardial Fibroelastosis; Female; Heart Failure; Hemodynamics; Humans; Hyponatremia; Middle Aged; Renin; Ultrafiltration; Uremia

We compared plasma ANF concentration in 5 diabetic-uremics with combined sympathetic-parasympathetic dysfunction with that in 9 uremic patients without autonomic impairment. Symptomatic dialysis hypotension was a major clinical problem in all diabetic-uremics. In the volume-expanded state, ANF was almost twice as high (p less than 0.025) in diabetic-uremics than in control uremics (152 +/- 29 vs 84 +/- 10 pg/ml) in the face of similar right atrial pressure (14 +/- 3 vs 12 +/- 1 cm H2O). After isolated ultrafiltration, ANF fell significantly in both groups remaining slightly (NS) higher in diabetic-uremics. The slope of the relationship between ANF and right atrial pressure was significantly (p less than 0.01) steeper in diabetic-uremics than in control uremics. The data indicate that autonomic failure amplifies the effect of atrial stretching on plasma ANF in diabetic-uremics on chronic hemodialysis treatment.

Topics: Adult; Atrial Natriuretic Factor; Autonomic Nervous System Diseases; Blood Pressure; Diabetic Nephropathies; Diabetic Neuropathies; Humans; Male; Middle Aged; Renal Dialysis; Uremia

Plasma levels of atrial natriuretic peptide (ANP), renin activity (PRA), and endothelin (ET) are often elevated in uremic patients on hemodialysis treatment. The profile of these vasoactive hormones and their relationships with hemodynamic indices in patients on continuous ambulatory peritoneal dialysis (CAPD), however, are not clear. We therefore measured plasma concentrations of ANP, PRA, ET, together with parathyroid hormone (PTH) in 17 patients (mean age 38.5 years) on maintenance CAPD over a period of 12 weeks. Baseline ANP, PRA, and ET levels were significantly higher than those of healthy subjects, and no significant changes in these indices were observed over the 12 week period. There was a significant positive correlation between levels of plasma ANP and PRA [rank correlation coefficient, R(s) = 0.496, p less than 0.05] as has been reported in cardiac failure. Despite the absence of clinically overt heart failure, a significant proportion (approximately 50%) of our patients demonstrated evidence of myocardial dysfunction on echocardiography. Furthermore, a significant positive correlation was demonstrated between plasma ANP and left atrial size [R(s) = 0.61, p less than 0.01] and an inverse correlation existed between plasma ANP and the left ventricular ejection fraction [R(s) = 0.51, p less than 0.05]. Twelve patients (71%) had biochemical evidence of hyperparathyroidism with raised levels of serum PTH. Our study demonstrates increased levels of plasma ANP, PRA, and ET in uremic patients on long-term CAPD. A positive correlation exists between plasma ANP and PRA suggesting their myocardial function may be compromised and this was confirmed on echocardiography. The possibility that high circulating PTH concentrations contribute to impaired cardiac function in such patients, deserves further study.

Topics: Adult; Atrial Natriuretic Factor; Cardiomegaly; Echocardiography; Endothelins; Female; Humans; Male; Parathyroid Hormone; Peritoneal Dialysis, Continuous Ambulatory; Renin; Time Factors; Uremia

In 5 haemodialyzed patients the influence of 3 months' erythropoietin (EPO) treatment on plasma renin activity (PRA), aldosterone (Ald), vasopressin (AVP) and atrial natriuretic peptide (ANP) was studied. Results were compared with those obtained in 7 uraemic patients showing a similar haematocrit value as patients after EPO therapy and with those obtained in 10 healthy subjects. EPO treatment did not influence significantly blood pressure but was suppressing PRA and plasma Ald levels, and raising plasma ANP concentrations. EPO treatment was without influence on AVP plasma levels. Data obtained in this study suggest that EPO-induced endocrine alterations are not due to increased blood volume and only partially related to improvement of uraemic anaemia.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Erythropoietin; Hematocrit; Homeostasis; Hormones; Humans; Male; Middle Aged; Renal Dialysis; Renin; Uremia; Vasopressins

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in 43 non-dialyzed uremic patients at rest and during maximal exercise to assess the possible relationship between plasma ANP levels and cardiac function, as judged by M-mode echocardiography and exercise tolerance. Patients with poor exercise capacity (exercise time less than 6 min) on dynamic exercise test had decreased left ventricular ejection fraction, increased left atrial diameter, and increased left ventricular mass index (LVMI), compared with patients with better exercise capacity (exercise time greater than 6 min). Plasma ANP was significantly higher in patients with poor exercise capacity and impaired cardiac function (202 pg/ml [95% confidence interval 119 to 284] at rest and 227 pg/ml [149 to 304] during exercise), compared with patients with better exercise capacity (75 pg/ml [50 to 102], p less than 0.005, and 123 pg/ml [80 to 167], p less than 0.05, respectively). Plasma ANP increased significantly (p less than 0.005) during exercise only in patients with better cardiac function. The best correlation among the variables studied was found between LVMI and plasma ANP concentration at rest (r = 0.56, p less than 0.001) and during exercise (r = 0.51, p less than 0.005), whereas neither blood pressure nor renal function showed any significant correlation with ANP levels. We conclude that plasma ANP levels are elevated in uremic patients with impaired cardiac function, correlating with increased LVMI. Plasma ANP determinations are useful in identifying increased cardiac load and consequent cardiac hypertrophy and dysfunction with known associations with increased cardiovascular mortality in patients with chronic renal failure.

Topics: Adult; Aged; Atrial Natriuretic Factor; Echocardiography; Exercise Test; Female; Heart; Humans; Male; Middle Aged; Uremia

1. Eleven patients on chronic maintenance dialysis were investigated before and after intravenous bolus injection of atrial natriuretic peptide (2 micrograms/kg body weight). 2. Mean blood pressure was reduced to the same extent in the uraemic patients as in 11 healthy subjects, with a nadir 3 min after the atrial natriuretic peptide injection at which time mean blood pressure was reduced by 13% (median) in the uraemic patients and 11% in the healthy subjects. 3. Basal plasma atrial natriuretic peptide and guanosine 3':5'-cyclic monophosphate levels were higher in the uraemic patients than in the healthy subjects, but guanosine 3':5'-cyclic monophosphate increased markedly in both groups after atrial natriuretic peptide injection. 4. Using changes in gamma-emission from blood after previous labelling of erythrocytes with 51Cr, and changes in packed cell volume, haemoglobin and erythrocyte count, a reversible shift of fluid from the intravascular phase was demonstrated in the uraemic subjects. The blood volume was maximally reduced by 6% (median) of initial blood volume at 30 min after atrial natriuretic peptide injection. 5. Correlation analyses gave no evidence of a causal relationship between the changes in mean blood pressure and changes in blood volume, angiotensin II, aldosterone or arginine vasopressin after atrial natriuretic peptide injection. 6. It is concluded that a pharmacological dose of atrial natriuretic peptide reduces blood pressure in uraemic patients on maintenance dialysis to the same extent as in healthy subjects. The blood-pressure-reducing effect of atrial natriuretic peptide does not seem to be mediated by its diuretic effect or ability to displace fluid from plasma to the interstitial fluid compartment.

Topics: Adult; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cyclic GMP; Female; Heart Rate; Humans; Male; Middle Aged; Uremia

Renal response to release of bilateral ureteral obstruction resembles that to intravenous administration of atrial natriuretic peptide. In a prospective study we measured plasma atrial natriuretic peptide levels before and serially after relief of obstruction in 9 patients (mean age 65 +/- 2 years old) with bilateral ureteral obstruction and azotemia. Obstruction was documented by renal ultrasonography. Before relief of obstruction blood urea nitrogen and serum creatinine levels were 85 +/- 18 (mean +/- standard error) and 8.2 +/- 1.3 mg. per dl., respectively, accompanied by metabolic acidosis but not hyperkalemia. Mean plasma atrial natriuretic peptide (measured by radioimmunoassay) was 129 +/- 28, which was markedly elevated compared to 46 +/- 7 pg. per ml. in 7 age-matched control subjects (p less than 0.01). After relief of obstruction, prominent post-obstructive diuresis and natriuresis ensued; the plasma atrial natriuretic peptide level progressively decreased to that noted in the control group, accompanied by improvement in renal function, and diminishing diuresis and natriuresis. These findings were associated with a significant weight loss and an increase in plasma renin activity (from a mean of 1.57 +/- 0.68 to 5.27 +/- 1.82 ng. per ml. per hour, p less than 0.01). These results suggest that atrial natriuretic peptide release is augmented in patients with bilateral ureteral obstruction and azotemia, probably due to hypervolemia, and may contribute to post-obstructive diuresis and natriuresis.

Topics: Atrial Natriuretic Factor; Blood Urea Nitrogen; Creatinine; Female; Humans; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Uremia; Ureteral Obstruction; Water-Electrolyte Balance

To study the trigger for the release of atrial natriuretic peptide (ANP) in man, we measured the atrial areas (AA) by 2-D echocardiography, the total blood volume (TBV) by 131I-serum albumin and plasma immunoreactive ANP (i-ANP) concentrations by radioimmunoassay, after prior plasma extraction, for 10 dialyzed uremic patients. Measurements were made when the patients were volume-loaded or volume-depleted by isoosmotic ultrafiltration and again 48 h later, when they were again volume-loaded. Analysis of plasma extracts by high-performance gel permeation chromatography revealed that the greatest amount of the i-ANP fraction was a peptide eluting like human synthetic alpha-ANP. Ultrafiltration consistently decreased the TBV, while spontaneous regain of body-fluids caused TBV to rise to pre-ultrafiltration levels. Changes in TBV were closely related in time to changes in both right (RAA) and left (LAA) atrial area and in plasma i-ANP concentrations. Significant direct relationships were found between TBV and RAA, TBV and i-ANP and between both LAA and RAA and i-ANP. Furthermore, the decreases and the increases in TBV, RAA and LAA were closely correlated with changes in i-ANP. Multiple regression analysis, however, revealed that the changes in plasma i-ANP were mainly related to the changes in RAA, with little or no relationship to the changes in TBV or LAA. These findings are evidence for a positive feed-back between the level of intravascular filing volume, extent of atrial distention and amount of i-ANP released into the blood stream.

Topics: Adult; Atrial Natriuretic Factor; Blood Volume; Female; Heart Atria; Humans; Male; Middle Aged; Renal Dialysis; Uremia

A highly sensitive radioimmunoassay for alpha-human atrial natriuretic peptide (alpha-hANP) was established and applied to measure the human plasma alpha-hANP levels. In our assay system, anti-alpha-hANP antiserum was raised in albino rabbits by intradermally injecting synthetic alpha-hANP which was conjugated with bovine serum albumin. The final antiserum dilution was 1:50,000. Sensitivity was 2 pg/tube and the 50% intercept was at 28 pg/tube. The plasma alpha-hANP was extracted using a Sep-Pak C-18 cartridge. According to this procedure, the mean recovery was 73.8 +/- 3.4% (mean +/- SE). The averaged plasma levels of immunoreactive alpha-hANP (i alpha-hANP) in normal subjects were 24.8 +/- 2.1 pg/tube. In patients with chronic renal failure undergoing hemodialysis, the averaged plasma i alpha-hANP levels were 56.4 +/- 5.0 pg/ml before hemodialysis. Plasma i alpha-hANP levels were significantly higher in the patients with chronic renal failure than in the normal subjects. After hemodialysis, plasma i alpha-hANP levels decreased significantly (32.2 +/- 2.8 pg/ml). These results suggest that the alteration in extracellular fluid volume (ECFV) may affect the plasma levels of i alpha-hANP in patients with chronic renal failure under hemodialysis; i.e., an increase in ECFV elevates and a decrease in ECFV lowers the circulating levels of alpha-hANP.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Humans; Middle Aged; Rabbits; Radioimmunoassay; Renal Dialysis; Uremia

Basal plasma alpha-human natriuretic peptide (alpha-hANP) values were found to be significantly higher in 7 fluid-overloaded chronic dialysis patients than in 13 non-dialysed renal patients without extracellular fluid (ECF) expansion. Iso-osmotic reduction of the body weight by a single 3-h ultrafiltration caused alpha-hANP to decrease significantly in all anuric patients to values comparable to those of non-dialysed subjects. In this latter group, however, there was a significant inverse relationship between alpha-hANP and glomerular filtration rate but not between alpha-hANP and total blood volume. These findings suggest that both ECF expansion and impaired renal removal of alpha-hANP might be responsible for the high alpha-hANP in chronic uraemia.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Kidney Function Tests; Male; Middle Aged; Renal Dialysis; Uremia; Water-Electrolyte Balance

Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay in 10 patients with end-stage renal failure during two successive 150-min periods of ultrafiltration and perfusion of an identical fluid volume (1,800-2,400 ml). The patients were divided into two groups of 'denervated' and 'intact' patients based on three different tests for cardiac parasympathetic dysfunction. Plasma ANP was higher in the denervated group than in the intact group throughout all the study, but decreased with the volume ultrafiltered and increased with the volume perfused in both groups. The sensitivity of ANP response to perfusion was greater in denervated than in intact patients. These results demonstrate the close relationship between plasma ANP and stepwise decremental or incremental changes in extracellular fluid volume. They also suggest that cardiac parasympathetic innervation plays a role in modulation of ANP secretion in humans.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Extracellular Space; Female; Heart; Humans; Kidney Failure, Chronic; Male; Middle Aged; Parasympathetic Nervous System; Plasma Volume; Ultrafiltration; Uremia

Serum ANP levels were measured by radioreceptor assay in 40 patients with various forms of secondary hypertension and 6 patients with heart failure. In addition, serum ANP was determined in 4 patients with renal artery stenosis before and after dilatation, as well as in 5 anephric patients before and after haemodialysis. Our results showed elevated serum ANP level in most patients with various forms of secondary hypertension and chronic heart failure. A distinction between these two groups and a control group of healthy individuals was not possible due to the wide range and occasional normal levels in the first two groups. ANP levels in patients with renal stenosis decreased after dilatation but there was no correlation with the success of this procedure. A positive correlation between ANP and plasma renin level was detectable in patients with renal artery stenosis, but was also elevated in anephric patients with absent renin production. In summary, our results show that measurements of serum-ANP are of little significance in the diagnosis of hypertension and chronic cardiac failure.

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Hypertension; Radioligand Assay; Renal Artery Obstruction; Renal Dialysis; Renin; Uremia

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Animals; Atrial Natriuretic Factor; Cattle; Cells, Cultured; Glucocorticoids; Humans; Mineralocorticoids; Uremia

We have investigated the influence of body fluid volume status on plasma levels of immunoreactive atrial natriuretic peptide (irANP) in eight uraemic patients on chronic haemodialysis, including two diabetics with severely impaired reflex control of the heart. IrANP was significantly higher in volume-expanded uraemic patients (36 +/- 16 pg/ml) than in a group of seven age and sex-matched normal subjects (14 +/- 2 pg/ml), and fell consistently, approaching the normal range after the removal of 2.0-4.3 litres of isotonic plasma ultrafiltrate (by isolated ultrafiltration). Plasma levels of the hormone were strictly related to right atrial pressure. The irANP response to ultrafiltration in the two diabetics was similar to that of the other uraemic patients. The results suggest that the elevated irANP levels found in volume-expanded uraemic patients depend largely on fluid overload per se. The preserved irANP response to ultrafiltration of the two diabetics with severe autonomic neuropathy indicates that in chronic renal failure irANP secretion may be regulated independently from autonomic influences.

Topics: Adult; Atrial Natriuretic Factor; Diabetic Neuropathies; Dysautonomia, Familial; Humans; Male; Middle Aged; Renal Dialysis; Ultrafiltration; Uremia