Lack of atrial natriuretic peptide receptors in human aldosteronoma

The effect of synthetic alpha-human atrial natriuretic peptide (ANP) on aldosterone secretion was studied in human aldosterone producing adrenocortical adenoma obtained surgically from a patient with primary aldosteronism and in human apparently normal adjacent adrenal cortical tissues obtained from a patient with pheochromocytoma, in vitro. Apparently normal adrenal cortical tissue responded to ANP with the known inhibition of aldosterone secretion. In contrast, the aldosterone producing adenoma did not respond to ANP. When stimulated by either ACTH or angiotensin II, there is no inhibition by ANP in the adenoma tissue, whereas normal tissue was inhibited. Immunohistochemical examination utilizing an ANP-receptor antiserum demonstrated that there was no evidence of binding site in the cortical adenoma, in contrast, zona glomerulosa cells in the cortical tissues adjacent to either aldosterone producing adenoma or pheochromocytoma were densely stained. This apparent lack of ANP-receptors is an associated finding with the hypersecretion of aldosterone in the aldosterone producing adenoma.     

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.     

A diurnal plasma vasopressin rhythm in rats

The purpose of this paper was to determine whether there is a diurnal plasma arginine vasopressin (AVP) rhythm in rats. Using an AVP radioimmunoassay, plasma AVP levels were determined at frequent intervals throughout a 24-hour period in adult male rats. Our data revealed a diurnal rhythm in plasma AVP levels, with mid-afternoon and early evening levels significantly greater than those in the morning and late evening.     

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.     

Evaluation of atrial natriuretic peptide and brain natriuretic peptide in atrial granules of rats with experimental congestive heart failure.

The natriuretic peptides are believed to play an important role in the pathophysiology of congestive heart failure (CHF). We utilized a quantitative cytomorphometric method, using double immunocytochemical labeling, to assess the characteristics of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in atrial granules in an experimental model of rats with CHF induced by aortocaval fistula. Rats with CHF were further divided into decompensated (sodium-retaining) and compensated (sodium-excreting) subgroups and compared with a sham-operated control group. A total of 947 granules in myocytes in the right atrium were analyzed, using electron microscopy and a computerized analysis system. Decompensated CHF was associated with alterations in the modal nature of granule content packing, as depicted by moving bin analysis, and in the granule density of both peptides. In control rats, the mean density of gold particles attached to both peptides was 347.0 +/- 103.6 and 306.3 +/- 89.9 gold particles/microm2 for ANP and BNP, respectively. Similar mean density was revealed in the compensated rats (390.6 +/- 81.0 and 351.3 +/- 62.1 gold particles/microm2 for ANP and BNP, respectively). However, in rats with decompensated CHF, a significant decrease in the mean density of gold particles was observed (141.6 +/- 67.3 and 158.0 +/- 71.2 gold particles/microm2 for ANP and BNP, respectively; p<0.05 compared with compensated rats, for both ANP and BNP). The ANP:BNP ratio did not differ between groups. These findings indicate that the development of decompensated CHF in rats with aortocaval fistula is associated with a marked decrease in the density of both peptides in atrial granules, as well as in alterations in the quantal nature of granule formation. The data further suggest that both peptides, ANP and BNP, may be regulated in the atrium by a common secretory mechanism in CHF.     

Release of atrial natriuretic peptide by atrial distension

A heterologous radioimmunoassay was used to measure the concentration of immunoreactive atrial natriuretic peptide (iANP) in plasma from the femoral artery of eight chloralose anaesthetized dogs. Mitral obstruction which increased left atrial pressure by 11 cmH2O increased plasma iANP from 97 +/- 10.3 (mean +/- SE) to 135 +/- 14.3 pg/mL. Pulmonary vein distension increased heart rate but did not increase plasma iANP. Bilateral cervical vagotomy and administration of atenolol (2 mg/kg) did not prevent the increase in iANP with mitral obstruction. Samples of blood from the coronary sinus had plasma iANP significantly higher than simultaneous samples from the femoral artery confirming the cardiac origin of the iANP. Release of iANP depends on direct stretch of the atrium rather than on a reflex involving left atrial receptors.     

Aging and photoperiod affect the daily rhythm pattern of atrial natriuretic peptide in the rat atrium

This study investigates the release characteristics of atrial natriuretic peptide (ANP) from young (10 weeks) and old (22 months) rat atrium. Levels of ANP release from samples of atrium were studied by organ perifusion. Rats were exposed to light:dark (LD) cycles of 12:12 or 18:6 and sacrificed at different zeitgeber time (ZT) points: ZT0, ZT6, ZT8, ZT12, ZT16, and ZT19 for LD 12:12 or ZT0, ZT9, ZT16, ZT18, ZT20, and ZT 21.5 for LD 18:6. The heart was collected, and the right atrium was removed, weighed, and perifused with Krebs-bicarbonate buffer for 100 min, including a period of 50 min for stabilization of secretion rate. ANP concentrations released by atrium did not differ between the two age groups either under LD 12:12 or under LD 18:6, except at the light:dark transition under LD 12:12 conditions where ANP levels were significantly (P < 0.05) lower in young compared to old rats. ANP exhibited daily variations in concentrations under LD 12:12, with a peak during the beginning of photophase (ZT0) in young rats and a peak at the beginning of scotophase (ZT12) in old animals. These variations were strongly modified under LD 18:6, where the pattern of the release exhibited a peak during the light phase at ZT16 in both young and old rats. This strongly suggests that the atrial ANP rhythm is dependent on the environmental light:dark cycle. Moreover, the total ANP levels released by atria in old rats were significantly increased under LD 18:6 compared to standard LD 12:12. This observation strongly suggests that old animals are more sensitive to a photoperiodic change. In conclusion, our results show that ANP concentrations in the rat atrium exhibit daily variations which are significantly affected by the daylength (photoperiod) change in aged rats.     

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.     

Regulation of atrial natriuretic peptide release in normal humans.

Atrial volume, pressure, and heart rate are considered the most important modulators of atrial natriuretic peptide (ANP) release, although their relative role is unknown. Continuous positive-pressure breathing in normal humans may cause atrial pressure and atrial volume to go in opposite directions (increase and decrease, respectively). We utilized this maneuver to differentially manipulate atrial volume and atrial pressure and evaluate the effect on ANP release. Effective filling pressure (atrial pressure minus pericardial pressure) was also monitored, because this variable has been proposed as another modulator of ANP secretion. We measured right atrial (RA) pressure, RA area, esophageal pressure (reflection of pericardial pressure), and RA and peripheral venous ANP in seven healthy adult males at rest and during continuous positive-pressure breathing (19 mmHg for 15 min). Continuous positive-pressure breathing decreased RA area (mean +/- SE, *P less than 0.05) 13.6 +/- 1.1 to 10.5 +/- 0.8* cm2, increased RA pressure 4 +/- 1 to 16 +/- 1* mmHg, increased esophageal pressure 2 +/- 1 to 12 +/- 1* mmHg, and increased effective filling pressure 2 +/- 0 to 4 +/- 1* mmHg. RA ANP increased from 67 +/- 17 to 91 +/- 18* pmol/l and peripheral venous ANP from 43 +/- 4 to 58 +/- 6* pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

Passive heat exposure leads to delayed increase in plasma levels of atrial natriuretic peptide in humans.

The effects of passive heat exposure on atrial natriuretic peptide (ANP) were studied in six healthy men staying in a Finnish sauna at +92 degrees C for 20 min. Their rectal temperature increased by 0.4 degrees C, and evaporative water loss was 0.92 +/- 0.14 (SD) kg. Heart rate and systolic blood pressure increased significantly during the 20-min exposure. Serum osmolality and plasma arginine vasopressin levels increased during the exposure, then declined, and increased significantly again at 90-120 min. Plasma renin activity and aldosterone increased by two- to fourfold in 20 min. Plasma ANP levels rose from 13 +/- 7 to 39 +/- 15 ng/l at 60 min and to 41 +/- 13 ng/l at 120 min (P less than 0.01 for both). We conclude that transient increases in heart rate and systolic blood pressure or changes in blood volume as inferred from the weight loss do not contribute to the increased plasma ANP levels observed after the heat exposure. Instead, increased secretions of pressor hormones could explain the elevated plasma ANP levels observed after the thermal stress.     

血管钠肽、 C型钠尿肽和心房钠尿肽舒血管作用的对比

本实验采用离体血管灌流方法,观察和比较血管钠肽（ＶＮＰ）,Ｃ型钠尿肽（ＣＮＰ）和心房钠尿肽（ＡＮＰ）对大鼠肺动脉,腹主动脉和腹腔静脉的舒张作用。．结果表明,ＶＮＰ,ＣＮＰ和ＡＮＰ对离体大鼠的保留内皮与去内皮的肺动脉,腹主动脉和腹腔静脉均有浓度依赖性舒张作用。     

Metabolic clearance rate and plasma half life of alpha-human atrial natriuretic peptide in man

The disappearance and metabolic clearance rate (MCR) of alpha human atrial natriuretic peptide (alpha h-ANP) has been studied in normal man by radioimmunoassay of the atrial peptide in plasma and plasma extracts. After an intravenous (iv) bolus injection of 100 micrograms alpha h-ANP, levels of immunoreactive alpha h-ANP (IR-alpha hANP) in unextracted plasma fell rapidly and exponentially during the first 10 min (t1/2 = 2.5 min), after which levels declined more slowly to reach basal values 30 min after injection. Venous plasma extracts, purified by Sep Pak cartridges, were used to calculate the MCR of IR-alpha hANP under steady state conditions of constant iv infusion (200 micrograms over 60 min) in healthy volunteers. Calculated MCR from venous samples was 2.4 L/min and volume of distribution 10.7 L. After cessation of infusions, the disappearance rate (rapid phase) of IR-alpha hANP was 3.1 min. These studies show that alpha h-ANP is rapidly metabolized at rates similar to other vasoactive hormones such as angiotensin II and vasopressin.     

Brain natriuretic peptide is cosecreted with atrial natriuretic peptide from porcine cardiocytes

Using primary cultures of atrial cardiocytes from neonatal pig, the secretion brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP)-like immunoreactivities (LI) was studied in vitro. Porcine cardiocytes time-dependently secreted both BNP-LI and ANP-LI into medium under a serum-free condition, although the amount of BNP-LI secreted was about one-third that of ANP-LI. Phorbol ester and Ca2+ ionophore had less stimulatory effects on secretion of BNP-LI than that of ANP-LI. Reverse-phase HPLC of the conditioned medium revealed a single major BNP-LI component corresponding to synthetic porcine BNP(1-26). These data suggest that a small molecular weight form BNP, possibly BNP(1-26), is cosecreted with ANP from porcine cardiocytes.