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To define the relation between atrial pressures and the release of atrial natriuretic peptide, we measured plasma concentrations of the peptide in 26 patients with cardiac disease--11 with normal atrial pressures and 15 with elevated atrial pressures (11 of these 15 had elevated pressures in both atria). Mean peptide levels (+/- SEM) in the peripheral venous blood were increased in the 11 patients with cardiac disease and normal atrial pressures, as compared with 60 healthy controls (48 +/- 14 vs. 17 +/- 2 pmol per liter). In the patients with elevated atrial pressures, peptide concentrations were increased twofold in peripheral venous, right atrial, pulmonary arterial, and systemic arterial plasma, as compared with the concentrations in the patients with normal atrial pressures. A step-up in peptide concentration was seen between the venous and right atrial plasma (P less than 0.002) and between the pulmonary and systemic arterial plasma (P less than 0.01), suggesting release of the peptide from the atria. A linear relation was found between right atrial pressure and right atrial peptide concentration (r = 0.835, P less than 0.001) and between pulmonary wedge pressure and the systemic arterial peptide concentration (r = 0.866, P less than 0.001). Right atrial pressure and the peptide concentration both increased with exercise testing in the nine patients evaluated. We conclude that the release of atrial natriuretic peptide is at least partly regulated by right and left atrial pressures. Distinguishing the relative contributions of the two atria and defining the role of peptide release in the pathogenesis of heart failure will require further investigation.
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PMID:Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. 294 77

Plasma levels of atrial natriuretic peptide (ANP) were measured in 9 patients with primary aldosteronism and 41 patients with essential hypertension (class I or II by WHO classification) using a specific and sensitive RIA. The mean plasma ANP concentration in patients with primary aldosteronism (mean +/- SEM, 67.1 +/- 10.8 pg/ml; n = 9) was significantly higher than that in healthy normotensive subjects (37.9 +/- 1.4 pg/ml; n = 108) or patients with essential hypertension (38.5 +/- 2.8 pg/ml; n = 41). During treatment with spironolactone, plasma levels of ANP declined in 6 of the 7 patients with primary aldosteronism, but no change occurred in the remaining patient who had cardiac enlargement of unknown etiology. The mean plasma ANP concentration in patients with essential hypertension, on the other hand, was not significantly different from that in normal subjects. These results indicate that plasma ANP levels are elevated in patients with primary aldosteronism, probably due to volume expansion, whereas no abnormality in ANP secretion exists in patients with uncomplicated essential hypertension.
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PMID:Plasma levels of atrial natriuretic peptide in primary aldosteronism and essential hypertension. 294 53

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.
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PMID:Plasma levels of atrial natriuretic peptide in patients with chronic renal failure. 294 54

To determine whether atrial natriuretic peptide (ANP) is a circulating hormone in the human fetus, ANP levels in umbilical cord plasma obtained at the time of delivery in 10 normal infants were measured by RIA. Plasma ANP levels were consistently higher in paired umbilical cord arterial than in cord venous samples. The mean umbilical cord arterial plasma ANP concentration [283 +/- 56 (+/- SEM) pg/ml] was significantly higher than that in cord venous plasma (165 +/- 27 pg/ml) or maternal peripheral venous plasma (155 +/- 25 pg/ml). Analyses by reverse phase high performance liquid chromatography revealed that the elution pattern of plasma ANP in cord arterial blood and that in maternal venous blood were nearly identical and that the retention time of the main ANP peak coincided with that of alpha-human ANP. These results suggest that alpha-human ANP is a circulating hormone in the human fetus.
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PMID:Atrial natriuretic peptide in umbilical cord blood: evidence for a circulating hormone in human fetus. 294 14

The vasodilating potency of alpha-human atrial natriuretic peptide (alpha-hANP) was investigated in the forearms of 16 normotensive subjects, 22 to 48 (mean 28) years old, with the use of venous occlusion plethysmography. alpha-hANP, 0.005 to 1.5 micrograms/min/100 ml forearm volume (FAV), infused in nine dose steps into the brachial artery increased forearm blood flow (FAF; ml/min/100 ml FAV) from 2.8 +/- 0.4 (SEM) to a maximum of 9.6 +/- 1.1. Forearm vascular resistance (mean arterial pressure/FAF) decreased by 72%. The alpha-hANP dose that produced a 50% vasodilator response was 0.093 +/- 0.016 microgram/min/100 ml FAV (n = 11) and it resulted in a venous plasma concentration of ANP (pANP) of 115 +/- 7 pmol/liter (normal 2 to 80; radioreceptor assay). Intraindividually, the maximum dose of alpha-hANP induced an increase in FAF that was 60% of the maximum response to sodium nitroprusside (14.1 +/- 1.8). Combined infusions (n = 9) of maximum forearm vasodilator doses of alpha-hANP and nitroprusside increased FAF to 22.7 +/- 3.4; this additive vasodilator effect of alpha-hANP and nitroprusside is consistent with their different actions on the guanylate cyclase system. In man, the direct vasorelaxant effect of alpha-hANP occurs at concentrations within the upper normal range of pANP, suggesting a physiologic vasodilator role for alpha-hANP.
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PMID:The vasodilator potency of atrial natriuretic peptide in man. 294 42

Endogenous alpha-atrial natriuretic peptide (ANP) in plasma is elevated in various hypervolaemic conditions. Possible relationships between circulating immunoreactive ANP and cardiovascular and splanchnic haemodynamics were therefore studied in patients with cirrhosis (n = 16) and controls (n = 12). Arterial plasma concentration of ANP in supine patients was (mean +/- SEM) 33 +/- 4 vs 41 +/- 10 pg/ml (9.9 +/- 1.2 vs 12.3 +/- 3.0 fmol/l) in controls (n.s.), and there was a weak direct correlation with right atrial pressure (r = 0.36, P = 0.05). There was no relationship with the presence of ascites or diuretic treatment. Central blood volume (CBV, i.e. the blood volume in the heart cavities, lungs, and aorta), determined from the mean transit time of 125I-labelled of 125I-labelled albumin and cardiac output, was significantly reduced in cirrhotics compared to controls (1.45 +/- 0.12 vs. 1.83 +/- 0.10 l, P less than 0.02) and inversely correlated with portal pressure (r = 0.42, P less than 0.05), whereas total plasma volume was somewhat increased (3.51 +/- 0.2 vs. 3.19 +/- 0.2, 0.05 less than P less than 0.1). A high arterio-venous extraction of ANP was found in the splanchnic system (extraction ratio 0.44 vs 0.28), kidney (0.45 vs 0.54), lower limb (0.53 vs 0.40), and forearm (0.27 vs 0.18) in patients and controls, respectively (n.s.). Our results suggest that the lack of elevation of circulating ANP in cirrhosis, even in the presence of actual fluid retention, may be explained by central hypovolaemia in these patients. Turnover and degradation of ANP is rapid and normal, as evaluated from the tissue extraction ratios.
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PMID:Circulating atrial natriuretic peptide (ANP) and central blood volume (CBV) in cirrhosis. 295 59

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5 +/- SEM 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 +/- 2.4 pg/ml) to day 7 (15.1 +/- 2.6 pg/ml). The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium 'escape' occurred by days 4 to 7. These results support the concept that ANP could play an important hormonal role in over-coming the sodium-retaining effects of mineralocorticoids in man.
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PMID:Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man. 295 26

We studied the effect of an increase in heart rate and/or in right atrial pressure (RAP) on the release of atrial natriuretic peptide (ANP) in 18 patients. In group 1 (n = 6), right ventricular stimulation (100, 120, 140 and 150 bpm) was used to increase RAP by asynchronous contraction of the right atrium and ventricle. Mean RAP increased from 3.9 +/- 0.2 to 8.3 +/- 0.6 mmHg (mean +/- SEM). Median ANP levels increased from 120 to 440 pg ml-1 (P less than 0.05). In group 2 (n = 6), right atrial stimulation below 140 bpm did not have any effect on ANP or RAP, but at a rate above 140 bpm RAP increased from 5.8 +/- 0.5 to 7.5 +/- 0.5 mmHg and ANP from 226 to 396 pg ml-1 (P less than 0.05). In group 3 (n = 6), RAP or ANP were not influenced by continuous right atrial stimulation at 110 bpm. Plasma cyclic GMP levels paralleled the changes in plasma ANP. Thus, an acute increment of RAP results in a release of ANP, but acceleration of heart rate alone has no effect on ANP secretion.
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PMID:Acute increase in right atrial pressure by intracardiac stimulation releases atrial natriuretic peptide. 295 1

A sensitive and specific procedure for the measurement of atrial natriuretic peptide (ANP) in human plasma by radioreceptor assay, using bovine adrenal membranes treated with Triton-X-100, is described. Plasma levels (mean +/- SEM) of ANP in healthy subjects on a normal sodium intake were 8.4 +/- 1.4 pg/ml and could be modified by changes in sodium intake with increases in sodium intake being associated with higher levels. Mean plasma ANP was approximately 2-fold higher in patients with essential hypertension and 4-fold higher in patients with cardiac or renal disease. The values obtained were comparable in magnitude to those obtained by radioimmunoassay and there was a strong correlation (r = 0.94; p less than 0.001) between the values obtained by radioimmuno- and radioreceptor-assay. These results suggest that circulating ANP corresponds to the biologically active peptide and point to an important role of the atrial peptides in the control of sodium balance.
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PMID:Atrial natriuretic peptide in human plasma--comparison of radioreceptor versus radioimmunoassay. 295 62

The relative contribution of increased blood pressure (BP) or norepinephrine (NE), or both, to the stimulatory effect of an NE pressor infusion on circulating immunoreactive atrial natriuretic peptide (ANP) was evaluated in 10 healthy young men. They were studied during an infusion of NE, which was applied initially alone and then in combination with sodium nitroprusside. NE infusion rate was increased in four 30-minute intervals to a final dose of 200 ng/kg body weight per minute, leading to 12-fold higher plasma NE levels than were seen during control conditions. This increased mean BP (from a mean basal value of 94 +/- 3 to 119 +/- 4 [SEM] mm Hg; p less than 0.001) and plasma immunoreactive ANP (from 50 +/- 7 to 112 +/- 17 pg/ml; p less than 0.001), whereas heart rate decreased (p less than 0.001). The NE infusion was continued at the highest dose and an additional infusion of sodium nitroprusside was started to titrate mean BP in 30-minute intervals down to control values; a mean sodium nitroprusside dose of 0.95 micrograms/kg/min restored mean BP to 93 +/- 4 mm Hg (p less than 0.001), decreased plasma immunoreactive ANP to basal values (51 +/- 4 pg/ml; p less than 0.001), increased heart rate (p less than 0.001), and left plasma levels of NE largely unchanged. Plasma protein and hematocrit rose about 5 to 6% (p less than 0.001) during the NE infusion and then decreased about 3 to 4% (p less than 0.001 and p less than 0.01) when sodium nitroprusside was added.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pressure dependence of atrial natriuretic peptide during norepinephrine infusion in humans. 295 21


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