Rise In Plasma Atrial Natriuretic Peptide Research Articles

Atrial natriuretic peptide contribution to lipid mobilization and utilization during head-down bed rest in humans

Head-down bed rest (HDBR) increases plasma levels of atrial natriuretic peptide (ANP) and decreases norepinephrine levels. We previously demonstrated that ANP promotes lipid mobilization and utilization, an effect independent of sympathetic nervous system activation, when infused into lean healthy men at pharmacological doses. The purpose of the present study was to demonstrate that a physiological increase in ANP contributes to lipid mobilization and oxidation in healthy young men. Eight men were positioned for 4 h in a sitting (control) or in a HDBR position. Indexes of lipid mobilization and hormonal changes were measured in plasma. Extracellular glycerol, an index of lipolysis, was determined in subcutaneous adipose tissue (SCAT) with a microdialysis technique. A twofold increase in plasma ANP concentration was observed after 60 min of HDBR, and a plateau was maintained thereafter. Plasma norepinephrine decreased by 30-40% during HDBR, while plasma insulin and glucose levels did not change. The level of plasma nonesterified fatty acids was higher during HDBR. SCAT lipolysis, as reflected by interstitial glycerol, as well as interstitial cGMP, the second messenger of the ANP pathway, increased during HDBR. This was associated with an increase in blood flow observed throughout HDBR. Significant changes in respiratory exchange ratio and percent use of lipid and carbohydrate were seen only after 3 h of HDBR. Thus the proportion of lipid oxidized increased by 40% after 3 h of HDBR. The rise in plasma ANP during HDBR was associated with increased lipolysis in SCAT and whole body lipid oxidation. In this physiological setting, independent of increasing catecholamines, our study suggests that ANP contributes to lipid mobilization and oxidation in healthy young men.

Meuroendocrine Effects of a Short-Term Osmotic Stimulus in Patients with Chronic Schizophrenia

We studied the effects of a short-term hypertonic stimulus on plasma levels of the stress hormones adrenocorticotropin (ACTH), cortisol, prolactin, and the blood volume-and electrolyte-controlling hormones arginine vasopressin (AVP) and atrial natriuretic peptide (ANP). Seven patients suffering from chronic schizophrenia with negative symptoms and ten healthy control subjects were investigated by a 20-rninute infusion of 10 ml/kg body weight of hypertonic (2.5%) versus isotonic (0.9%) saline. All patients, who were medication-free for at least one week prior to the study, and all control subjects participated in two investigations in randomized order according to a single-blind cross-over design. During hypertonic infusion, plasma osmolarity and sodium levels were increased similarly in both groups and significantly more than during isotonic saline. Hypertonic saline caused a significant increase of plasma ACTH, cortisol and prolactin in patients in contrast to controls. AVP and ANP plasma concentrations were elevated after infusion of hypertonic saline, however, only patients showed a significant rise in plasma ANP. These results show that a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system in a subset of patients with chronic schizophrenia may become overt during an osmotic stimulation, indicating an increased sensitivity of patients with schizophrenia to osmotic stress.

Intrapericardial denervation: responses to water immersion in rhesus monkeys

Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P < 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P < 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P < 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P < 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

Influence of cardiopulmonary bypass on water balance hormones in children.

To determine the changes in the endocrine mechanisms of fluid balance after cardiopulmonary bypass in children. Prospective study; analysis of numbered plasma samples performed blind with respect to clinical data. Regional paediatric cardiothoracic unit. Nine patients, median age 4, range 2 to 9 years, five males. Patients under the age of 1 year were excluded because of the frequent blood sampling involved. Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin, plasma renin activity, aldosterone, noradrenaline and adrenaline, and urinary concentrations of cyclic guanosine monophosphate (cGMP) as measured by radioimmunoassay. After 30 minutes of cardiopulmonary bypass plasma atrial natriuretic peptide (ANP) decreased from (mean (SEM)) 151 (71) pg/ml to 52 (44) pg/ml (NS), and urinary production of its second messenger cyclic guanosine monophosphate (cGMP) decreased from 1286 (600) pmol/ml to 151 (414) pmol (p < 0.05). Other plasma concentrations of hormones studied did not change significantly although arginine vasopressin, adrenaline, and noradrenaline increased whereas aldosterone and plasma renin activity decreased. After cardiopulmonary bypass stopped there was an immediate and significant rise in plasma ANP, but within the next 24 hours plasma ANP declined significantly (p < 0.05), decreasing from 294 (49) pg/ml to 64 (29) pg/ml at 22 hours. In the postoperative period there was a significant correlation between plasma ANP and both mean fluid balance (r = 0.96, p < 0.001) and mean urine output (r = 0.97, p < 0.001). Plasma aldosterone peaked (p < 0.05) at 22 hours after operation, and argine vasopressin peaked (p < 0.05) at two hours and then declined (p < 0.05) to a trough at 24 hours. Plasma renin activity, adrenaline, noradrenaline, and urinary cGMP concentrations, and mean central venous pressure did not change significantly in the postoperative period. The changes documented show the differing pattern of release of water balance hormones invoked by cardiopulmonary bypass. The central role of ANP is shown by its strong correlation with urinary output and its similarly strong relation to fluid balance.

Effect of Saline Infusion on Urinary Calcium Excretion in Essential Hypertension

Urinary excretion of sodium and calcium was examined in hypertensive (n = 8) and normotensive (n = 7) subjects following infusion of 2% saline at a rate of 11 mL/min for 90 min. The urinary sodium excretion was 204 +/- 38 (mean +/- SEM) muEq/min in normotensives and 233 +/- 28 muEq/min in hypertensives before infusion of saline and increased maximally to 499 +/- 114 muEq/min (P less than .05) and to 928 +/- 68 muEq/min (P less than .01), respectively, after saline infusion. In normotensives, urinary calcium excretion did not change significantly; however, in hypertensives excretion increased markedly (P less than .01) from 6.1 +/- 0.7 muEq/min to 12.3 +/- 1.6 muEq/min. Plasma atrial natriuretic peptide (ANP) levels increased significantly (P less than .05) in both groups. Serum ionized calcium and plasma parathyroid hormone (PTH) levels did not change significantly. The increments of urinary sodium and calcium and of plasma ANP, as well as the preinfusion plasma PTH level, were significantly (P less than .05) higher in hypertensives than in normotensives. The present study showed that exaggerated natriuresis was accompanied by hypercalcinuria and an enhanced rise in plasma ANP in hypertensives. Basal levels of plasma PTH were elevated in hypertensives. The calcium deficiency may be attributable to a close relationship between urinary sodium and calcium, and causally related to the disturbance of sodium and volume homeostasis in hypertension, which results in exaggerated natriuresis.

Regulation of ANP secretion in insulin-dependent diabetes mellitus and the influence of autonomic neuropathy

In order to determine the effect of diabetic autonomic neuropathy (DAN) on the atrial natriuretic peptide (ANP) response to dynamic stimuli, we studied the ANP response to 60° head-up and 60° leg-up tilt in diabetic subjects with (DAN + ve, n = 8) and without (DAN − ve, n = 8) evidence of autonomic neuropathy and seven matched non-diabetic controls. Mean baseline plasma ANP concentrations were similar in all three groups. Head-up tilt was associated with a fall in plasma ANP in all seven healthy controls (21.8 (16.8–30.7) to 16.8 (7.1–29.1), P = 0.06, mean (range)), seven of the eight DAN − ve (16.9 (6.5–33.7) to 8.5 (3.0–21.1), P = 0.015) and all eight DAN + ve subjects (27.3 (8.5–101.5) to 15.4 (1.0–67.6), P = 0.044). Leg-up tilt caused a rise in plasma ANP in six of the seven healthy controls (17.6 (7.5–27.9) to 22.4 (15.2–48.1), P = 0.041), six of the eight DAN − ve (12.5 (7.8–27.8) to 15.5 (7.3–31.3), P = 0.054) and seven of the eight DAN + ve subjects (18.2 (2.8–55.1) to 25.1 (4.5–92.8), P = 0.013). There was no significant difference in the fall in plasma ANP during head-up tilt or in the rise in plasma ANP during leg-up tilt between the three groups. We conclude that the regulation of ANP secretion is normal in diabetes mellitus, and is unaffected by the presence of autonomic neuropathy.

Plasma Atrial Natriuretic Peptide in Elite Runners

Plasma atrial natriuretic peptide (ANP) was measured in relation to a 5-km race in 11 elite mid- and long-distance runners. Plasma ANP, measured in relation to the race, was compared with the relative changes in plasma volume and the physical fitness of the runners. Relative changes in plasma volume were estimated by changes in hemoglobin and hematocrit, and physical fitness was evaluated by a cycle ergometer test, running time, and resting heart-rate. In connection with the race, plasma ANP increased in all the runners. Median plasma ANP was 4.7 pmol.l-1 before the race and 12.9 pmol.l-1 immediately after the race. No correlation was found between the changes in ANP and the relative changes in plasma volume or the measurements of physical fitness. A volume expansion of the red blood cells was found immediately after the race. We conclude that well-conditioned subjects have a prominent rise in plasma ANP, in spite of a high maximal cardiac output.

Impact of acute and chronic sodium loading on atrial natriuretic peptide and renin in man

The relationship between the renin-angiotensin system and the atrial natriuretic peptide and its contributions to the control of sodium balance is not clarified. We therefore studied plasma renin concentration (PRC) and plasma levels of atrial natriuretic peptide (ANP) in normal subjects during acute and chronic salt loading. Acute intravascular volume expansion by iv infusion of 2000 ml of normal saline resulted in sharp rise in plasma ANP from 122 +/- 24 to 405 +/- 141 pg/ml (p less than 0.05). This increase was only transient with plasma ANP returning to control levels after 240 min. In contrast, reduction in plasma renin concentration was less pronounced, however it was persistent for up to 240 min paralleled by a reduction in plasma protein. Reciprocal changes in ANP plasma levels and PRC were observed during dietary modification in sodium intake. At the end of low sodium diet over 4 days, supine plasma ANP averaged 49 +/- 7 pg/ml and levels increased to 128 +/- 38 pg/ml after 6 days of high sodium intake in 11 healthy subjects (p less than 0.05). In contrast, PRC values averaged 69.8 +/- 19.8 microU/ml and 14.4 +/- 6.5 microU/ml during low and high sodium diet respectively (p less than 0.01). The inverse relation between PRC and ANP was seen after prolonged dietary sodium loading over 15 days in 8 additional subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide and total exchangeable body sodium: relationships in rats with chronic myocardial infarction.

1. The relationship between plasma atrial natriuretic peptide (ANP) and body sodium was determined in rats 1 month after myocardial infarction induced by coronary artery ligation. After operation rats received a normal or a low salt diet, and total exchangeable body sodium was measured sequentially. 2. Rats with infarction receiving a normal salt intake did not retain sodium when compared with sham-operated controls. Rats receiving a low salt diet had a 10% decrease in body sodium (P less than 0.01). The decrease was the same in rats with infarction as in controls. 3. Plasma ANP was similar in control rats irrespective of salt status. Plasma ANP levels were markedly elevated in rats with infarction irrespective of salt status (P less than 0.01). 4. The rise in plasma ANP was correlated with cardiac hypertrophy and infarct size in animals fed both normal and low salt diets. However, there was no relationship between plasma ANP and exchangeable body sodium. 5. These results suggest that in this model of heart failure plasma ANP is raised by increased left atrial stretch in proportion to the severity of left ventricular dysfunction. In contrast, plasma ANP concentrations do not appear to be elevated as a consequence of increased right atrial pressure caused by sodium retention and expanded extracellular volume.

Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man.

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.

REGULATION OF PLASMA ATRIAL NATRIURETIC PEPTIDE IN CHILDHOOD

A trial natriuretic peptide (ANP) is released from cardiac atria into circulation and induces diuresis and natriuresis. We studied plasma ANP in children using a sensitive radioimmunoassay. In 80 normal children aged 4 weeks to 16 years ANP averaged 27.8±14.0 fmol/ml (x̄±SD). Neonates had only slightly higher mean ANP levels, whereas in premature infants at day 1 of life ANP was up to 10 times higher than in normal children (252.6±210.0 fmol/ml, n:11). The increase in plasma volume Tnduoed by albumin infusion in children with nephrotic syndrome (n:9) caused a rise in plasma ANP from 36.1±22.6 to 151.4 ± 52.0 fmol/ml. ANP correlated with urine flow (r:0.64, p<0.01) and with sodium excretion (r:0.62, p<0.01). Reduction of volume overload by hemodialysis in children with chronic renal failure (n:14) resulted in a fall of elevated plasma ANP from 87.1±39.4 to 42.8± 26.0 fmol/ml (p < 0.001). This decrease correlated with concomitant reduction of body weight. These observations suggest that volume expansion is a potent stimulus of ANP release in children and that this hormone is important in volume homeostasis. Supported by Deutsche Forschungsgemeinschaft Ra 326/1-2

Atrial natriuretic peptide and volume changes in children.

The effect of volume changes on the plasma concentration of atrial natriuretic peptide (ANP) was investigated. In children with chronic renal failure predialysis plasma ANP was higher as compared to normal children and decreased significantly during hemodialysis. The decrease in plasma ANP correlated with body weight reduction. On the other hand, increase in plasma volume by infusion of albumin in children with nephrotic syndrome caused significant rise in plasma ANP and an increased natriuresis. Our data demonstrate that an expanded extracellular fluid volume and/or plasma volume appears to be a major stimulus for the release in ANP in children.