Human cardiac plasma concentrations of atrial natriuretic peptide quantified by radioreceptor assay

The presence of high affinity receptors for atrial natriuretic peptide in bovine adrenal cortex has enabled the development of a sensitive, specific and rapid radioreceptor assay for this peptide in human plasma. In 18 normal subjects, venous plasma atrial natriuretic peptide concentration ranged from 6 to 65 pM. This plasma concentration was two-fold higher in right atrium as compared to venous blood in 12 patients investigated by cardiac catheterisation, confirming that the right atrium is the site of release of atrial natriuretic peptide into circulation. There was a further step up in plasma atrial natriuretic peptide concentration between pulmonary arterial and aortic plasma. This finding indicates that released hormone in man may undergo further activation in the lungs, or that there may be direct release from the left atrium.     

Effect of different anesthetics on immunoreactive atrial natriuretic factor concentrations in rat plasma

The effect of different conditions of blood withdrawal and use of different anesthetics on immunoreactive atrial natriuretic factor (IR-ANF) concentrations in plasma was studied in rats. The concentration of IR-ANF in plasma from jugular vein of non-anesthetized conscious rats, cannulated either 24 hr before blood withdrawal was 93.9 +/- 17.1 pg/ml (n = 30); and 48 hr: 81.9 +/- 11.5 pg/ml (n = 29). Immobilization stress (4 hr) increased IR-ANF concentration: 248.0 +/- 80.2 pg/ml (n = 5). Anesthesia by morphine, diethyl-ether, chloral hydrate and ketamine chlorhydrate increased IR-ANF concentrations to 2,443.0 +/- 281.2 pg/ml (n = 24), 806.1 +/- 74.6 pg/ml (n = 64), 224.0 +/- 81.4 pg/ml (n = 20), and 195.0 +/- 20.3 pg/ml (n = 51), respectively. IR-ANF in plasma of sodium-pentobarbital and urethane anesthetized rats was 59.2 +/- 6.7 pg/ml (n = 10) and 42.6 +/- 8.1 pg/ml (n = 8), respectively. These changes in IR-ANF evoked by different types of anesthetics and different conditions of blood withdrawal have to be taken into consideration during studies on the physiopathological role of atrial natriuretic factor.     

Cardiac atrial natriuretic peptide concentrations in experimental obese mice

Obesity is usually associated with expansion of blood volume. Therefore, we studied whether obesity affects cardiac and plasma atrial natriuretic peptide (ANP) levels in experimental animal model. Mice made obese with gold thioglucose developed cardiac hypertrophy associated with increases in ANP in atrial tissue and plasma. There were significant (p less than 0.01) correlations between the cardiac ANP concentration and body weight or cardiac weight. These data suggest that enhanced synthesis of atrial ANP in obese mice can be mainly ascribed to increased blood volume associated with cardiac hypertrophy.     

Effect of exercise, hyperpnea, and bronchoconstriction on plasma atrial natriuretic peptide

To examine whether endogenous secretion of atrial natriuretic peptide (ANP) modifies the bronchomotor response to moderately strenuous exercise and, conversely, whether hyperpnea of exercise or bronchoconstriction alone modulates the release of ANP, we compared the rise in specific airway resistance and the rise in circulating immunoreactive ANP (IR-ANP) induced by a 5-min submaximal exercise and by eucapnic hyperpnea with cold dry air and exercise-matched minute ventilation in six healthy individuals and in five subjects with clinically stable asthma. As expected, the increase in specific airway resistance from base line provoked by exercise was greater in the asthmatic subjects (from 11.8 +/- 7.1 to 34.0 +/- 18.6 l.cmH2O.l-1.s-1) than in the healthy subjects (from 3.7 +/- 1.2 to 4.5 +/- 1.9 l.cmH2O.l-1.s-1). In both groups, exercise was associated with a similar and significant rise in plasma IR-ANP levels, ranging from 222 to 550% from base-line value in the healthy group and from 176 to 1,120% from base-line value in the asthmatic group. Peak plasma IR-ANP levels occurred from 3 to 15 min after completion of exercise with a return to base-line values within 60 min. Although eucapnic hyperpnea was associated with a similar increase in specific airway resistance as was exercise, it provoked an increase in circulating IR-ANP in only one subject.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of central hypertonic stimulation on plasma atrial natriuretic peptide and oxytocin in conscious rats

The effect of the intracerebroventricular (i.c.v.) injection of hypertonic sodium chloride on plasma atrial natriuretic peptide (ANP) and oxytocin (OT) was evaluated in conscious freely moving rats. A hypertonic or isotonic NaCl solution was injected into the third ventricle. Blood pressure and heart rate were monitored and blood samples were collected. I.c.v. injection of the hypertonic solution resulted in a significant increase in mean arterial pressure (105.3 +/- 2.9 mmHg at time 0 to 124.2 +/- 4.4 mmHg at 5 min, P less than 0.01) and heart rate (350.0 +/- 25.0 bpm at time 0 to 420.8 +/- 13.6 bpm at 20 min, P less than 0.01). Plasma OT increased 4-fold over the basal values 5 min after the injection (4.5 +/- 1.1 to 20.1 +/- 3.2 pg/ml, P less than 0.01), while there was no significant change in plasma ANP (37.3 +/- 9.1 to 46.6 +/- 12.6 pg/ml, n.s.). The control injection produced no significant changes in any parameters. These results show that hemodynamic changes are not necessarily associated with alterations in plasma ANP. Furthermore they suggest that central osmoreceptors are not involved in the control of ANP secretion.     

Lack of diurnal rhythm in plasma atrial natriuretic peptide.

The occurrence of a circadian rhythm in the concentration of circulating atrial natriuretic peptide (ANP) is not clearly established. To investigate diurnal changes, plasma levels of ANP were measured at 10-min intervals for 24 hours in six normal volunteers. The subjects were studied once during a normal sleep-wake cycle and once during a cycle with a shifted sleep period. They received continuous enteral nutrition from 8 hours preceding the experiment until the end of the experiment, throughout this time the subjects remained in a supine position. The mean ANP levels did not differ significantly between the sleep periods and the periods spent awake in either of the protocols, which provides evidence of a lack of a sleep-related influence of ANP. A significant linearity of the mean ANP profile was observed, smoothing out the transient and randomly occurring fluctuations in individual ANP concentration. These results lead to the conclusion that ANP secretion is neither under the control of endogenous circadian rhythmicity nor is it affected by sleep-regulatory mechanisms.     

Acute stress increases plasma concentrations of atrial natriuretic peptides

5 min exposure of inbred Maudsley Reactive male rats to intermittent foot-shock resulted in an approximate doubling of plasma atrial natriuretic peptides ANP (Control grp mean = 62.12 +/- 8.74; Stressed grp mean = 128.70 +/- 26.63 pg/ml) and 25 min exposure resulted in a three-fold increase (Stressed grp mean = 187.88 +/- 39.24 pg/ml). In the second experiment exposure of genetically heterogeneous Wistar male rats to 15 min of intermittent foot-shock produced a 10-fold increase in plasma ANP (Control grp mean = 45.76 +/- 6.05; Stressed grp mean = 471.20 +/- 58.49 pg/ml). The magnitude of the increase in plasma ANP produced by acute stress is as large as the increase caused by volume expansion and administration of various pharmacological agents and therefore delineation of biological role of ANP must take account of its potential role as a stress-hormone.     

Elevated plasma atrial natriuretic peptide in rats with myocardial infarcts

We measured atrial natriuretic peptide (ANP) plasma levels in rats with experimental heart failure caused by left coronary artery ligation. ANP levels were clearly higher in infarcted rats (409 +/- 59 pg/ml; mean +/- S.E.M.) than in sham-operated controls (39 +/- 6 pg/ml). Moreover, plasma ANP levels increased progressively with the severity of cardiac dysfunction and size of infarct. Increased release of ANP in post-infarction heart failure appears to be a meaningful compensatory response to control rising preload. Our results are in keeping with evidence from human studies showing increased plasma concentration of ANP in patients with congestive heart failure. This model is a useful tool to further explore the role of ANP in heart failure.     

Current indications of plasma atrial natriuretic peptide measurements in human diseases

The discovery of atrial natriuretic peptide (ANP) has modified our current understanding of the regulation of sodium metabolism. This peptide, of which the second messenger is cyclic guanosine monophosphate (cyclic GMP), is released by the atrial myocytes in response to increased atrial stretch and has for essential function to diminish the venous return to the heart. Radioimmunoassays have demonstrated that plasma ANP and cyclic GMP levels are increased in various diseases such as congestive heart failure (CHF), renal insufficiency, and, to a lesser extent, diabetes mellitus and liver cirrhosis with ascites. Plasma ANP is of prognostic value in CHF and reflects the effective central volemia in renal failure so that its assay as well as that of plasma cyclic GMP seem of interest in these diseases. Further studies are needed to assess the pathophysiological significance of ANP in diabetes mellitus and cirrhosis, and to define the indications of the treatment by enkephalinase inhibitors which increase endogenous ANP levels by lowering the catabolism of this hormone.     

Effect of atrial natriuretic peptide on adrenal renin and aldosterone

The effect of atrial natriuretic peptide (ANP) on adrenal renin and aldosterone was investigated in anesthetized rats. Under pentobarbital anesthesia 40 mg/kg), intravenous infusion of ANP (0.25 micrograms/kg/min) for 45 min failed to alter the adrenal renin, adrenal aldosterone, and plasma aldosterone (PA). In this condition, intraperitoneal injection of ACTH (10 micrograms/kg) significantly increased the adrenal renin (from 2.4 +/- 0.1 to 5.0 +/- 0.08 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 13.6 +/- 1.3 to 22.7 +/- 2.3 ng/mg protein, P less than 0.01) and PA (from 59.8 +/- 5.8 to 75.5 +/- 7.4 ng/dl, P less than 0.05), respectively. Under ACTH stimulation, ANP infusion induced significant decreases in adrenal renin (from 5.0 +/- 0.08 to 2.8 +/- 0.2 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 22.7 +/- 2.3 to 16.2 +/- 1.8 ng/mg protein, P less than 0.05) and PA (from 75.5 +/- 7.4 to 61.6 +/- 4.9 ng/dl). These results suggest a possible role for adrenal renin in the mechanism underlying the inhibitory effect of ANP on aldosterone production in vivo.     

Effect of atrial natriuretic peptide on bronchial tone in anesthetized rabbits

The effect of atrial natriuretic peptide (ANP) on histamine-induced bronchoconstriction was studied in vivo (in normoxic and in hypoxic rabbits) and in vitro. Thirty-two anesthetized rabbits, spontaneously breathing room air or 10% O₂, received infusions of ANP (20, 40, or 80 ng/min/kg normoxia; 20 ng/min/kg hypoxia) or the vehicle for 100 min. After 75 min of ANP infusion, bronchoconstriction was induced inhaling histamine; respiratory resistance (Rrs) was measured prior to and until 20 min posthistamine. The results show that the histamine-induced increase in Rrs was significantly reduced by ANP 80 ng/kg/min in normoxia, and by ANP 20 ng/kg/min in hypoxia. In vitro, ANP had no effect on tracheal and bronchial smooth muscle precontracted with histamine or acetylcholine. These results show that ANP can decrease a histamine-induced bronchoconstriction in vivo but not in vitro, suggesting an indirect mechanism of action.     

Nocturnal fluctuations of plasma atrial natriuretic peptide in normotensive and hypertensive men

Plasma levels of immunoreactive atrial natriuretic peptides (ANP) were measured at 10-min intervals during night-sleep in 4 normotensive and in 4 moderate, essential hypertensive subjects. The mean ANP levels ranged from 24.3 to 27.9 pg.ml-1 for the normal subjects. These mean levels were not significantly different in the hypertensive subjects (range: 26.3 to 37.2 pg.ml-1). Fluctuations, often of small amplitude, were observed around this mean, without any defined periodicity. Changes in plasma ANP were not associated with changes in heart rate. Analysis of the ANP profiles and the concomitant sleep stage patterns did not reveal any temporal relationship between ANP fluctuations and specific sleep stages or waking periods. The ANP profiles did not differ between the groups, which indicates no abnormality in ANP secretion in moderate essential hypertension.     

Effect of head-out immersion on plasma atrial natriuretic factor in man

This study was conducted to examine the role of atrial natriuretic factor (ANF) in the development of diuresis and natriuresis in response to the head-out immersion in 35 degrees C water. Six male subjects were hydrated (0.5% body wt), sat for 1 hr in air (preimmersion), were immersed in water to the neck for 3 hr, and then sat for 1 hr in air (postimmersion). In another series they were similarly hydrated and then sat for 5 hr in air for the time control. Urine and venous blood samples were collected hourly for creatinine and electrolyte measurements. In addition, the concentration of ANF was determined in unextracted plasma by a radioimmunoassay. The pattern of electrolyte excretion was evaluated on the basis of fractional excretion of filtered load. In the time control series, urine flow and fractional excretion of Na and K remained low throughout the 5-hr experimental period. On the other hand, urine flow increased significantly from the preimmersion level of approximately 2 to approximately 7 ml/min during the first hour of immersion (P less than 0.05), after which it decreased to approximately 5 ml/min during the second hour of immersion (P less than 0.05) and to approximately 2 ml/min during the third hour of immersion. Fractional excretion of Na increased continuously from preimmersion level of approximately 1.0 to approximately 1.8% during the second and third hours of immersion (P less than 0.05) and then decreased to 1.2% during the 1-hr postimmersion period. The plasma ANF remained low (approximately 75 pg/ml) during the 5-hr time control period. In the immersion series, plasma ANF increased significantly from the preimmersion level of approximately 80 to approximately 120 pg/ml during the entire 3-hr immersion period and then returned to the preimmersion level during 1 hr postimmersion. These results indicate that the immersion diuresis and natriuresis are indeed associated with the increased ANF release. However, it can not be ascertained from the present study if the increased ANF contributes directly to these renal responses to immersion or in concert with other mediators.     

Effect of atrial natriuretic factor on plasma vasopressin in conscious rats

An intravenous (IV) bolus injection (10 μg) of synthetic rat atrial natriuretic factor [ANF (Arg 101-Tyr 126)] into normal conscious Sprague-Dawley rats produced a significant decrease of plasma arginine vasopressin (AVP) while 1-, 2-, and 5-μg doses exerted no such effect. Mean arterial blood pressure (MAP) was lowered about 15 mmHg by an IV 10 μg bolus injection of ANF. When plasma AVP rose significantly in rats exposed to such osmotic stimuli as 600 mM NaCl and 900 mM mannitol intraperitoneally (IP), subsequent IV injection of ANF (10 μg) markedly depressed this parameter. Lower doses of ANF were ineffective against 600 mM NaCl IP. The significant elevation of plasma AVP levels by hypertonic sucrose 900 mM IP was not modified by ANF (10 μg). Blood pressure remained unchanged after IP administration of various osmotic stimuli, except mannitol, and in all these experiments an IV bolus of ANF exerted a lowering effect on MAP. Seventy-two hr water deprivation (mixed osmotic and volume stimulus) resulted in elevated plasma AVP levels which were unaffected by an IV bolus injection of ANF at doses of 0.06–10 μg. Immunoreactive ANF (IR-ANF) rose in plasma to 39.3±13 ng/ml 1 min after an IV bolus injection of 10 μg ANF, dropping to 1.01±0.2 ng/ml after 5 min and to 0.32±0.01 ng/ml after 10 min (when ANF and AVP interactions were studied), but still remained approximately six times higher than in control rats. These results suggest that, in the conscious rat, only pharmacological levels of ANF observed after an IV bolus infusion may influence both resting and osmotically-stimulated AVP levels.     

Effect of atrial natriuretic peptide on renin release in rat isolated glomeruli

Effects of atrial natriuretic peptide (ANP) on renin release in isolated rat glomeruli were investigated. ANP suppressed renin release by 25% at 5 x 10(-8) M when glomeruli were incubated in a medium containing 1.26 mM calcium (p = 0.0019). When glomeruli were incubated in a calcium free medium containing 2 mM EGTA, ANP suppressed stimulated renin release significantly at 5 x 10(-8) and 5 x 10(-9) M by 25% (p = 0.0204, and p = 0.0101, respectively). These results indicate that ANP suppresses renin release in a dose dependent manner, probably through a calcium independent process.     

Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptide

The effect of opiate ligand administration on plasma levels of atrial natriuretic peptide (ANP) was studied in awake, freely moving Sprague-Dawley rats. Prior to and following the intracerebroventricular (icv) or central venous (iv) injection of morphine (MS), leu-enkephalin (Leu-enk), dynorphin (Dyn) or beta-endorphin (B-endor), plasma samples were obtained for measurement of ANP concentrations by radioimmunoassay. MS was 10 times more potent when given icv than when given iv to increase plasma ANP levels. Icv injection of Leu-enk decreased plasma ANP concentrations. Dyn and B-endor administration (iv or icv) did not alter the plasma concentration of ANP. These effects of MS and Leu-enk on plasma concentrations of ANP appear to be mediated through actions on the central nervous system. MS, Leu-enk, B-endor, and Dyn given icv, produced elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. When MS was given icv, mean Epi and NE plasma levels increased 10-50 times the increases noted with B-endor, Leu-enk and Dyn. A role of catecholamines in mediating MS-stimulated ANP release is supported by the observation that ganglionic blockade with chlorisondamine significantly attenuated the increase of plasma ANP levels. MS, but not B-endor, Leu-enk and Dyn, acts within the brain to increase plasma levels of ANP. MS-induced elevations of plasma ANP levels may be dependent on an intact autonomic nervous system.     

The influence of carotid sinus pressure on plasma atrial natriuretic peptide in anaesthetized rabbits

The effect of changes in carotid sinus perfusion pressure on plasma immunoreactive atrial natriuretic peptide (IR-ANP) was examined in anaesthetized rabbits, and the role of arterial pressure in mediating the changes in IR-ANP was assessed. Plasma IR-ANP was significantly greater (101.7 +/- 24.3 pg ml-1) when carotid sinus pressure was 60 mmHg than when it was 160 mmHg (27.1 +/- 8.6 pg ml-1). Mean arterial pressure (MAP) was significantly greater when carotid sinus pressure was controlled at 60 mmHg compared to when it was 160 mmHg, but right atrial pressure (RAP) was not significantly different at the two carotid sinus pressures. The administration of hexamethonium attenuated the changes in MAP and heart rate (HR) which occurred in response to alterations in carotid sinus pressure, and abolished the change in plasma IR-ANP. The results suggest that an inverse relationship exists between carotid sinus pressure and plasma IR-ANP, and that the release of ANP in response to a reduction of carotid sinus pressure is mediated by the associated haemodynamic changes.