Changes in atrial natriuretic factor during preload reduction with nitroglycerin in patients with congestive heart failure

Nine patients with congestive heart failure, New York Heart Association class II-III, were evaluated with right heart catheterization. Plasma atrial natriuretic factor (ANF) was determined in blood samples from the pulmonary artery simultaneously with recordings of right atrial, pulmonary arterial, pulmonary capillary wedge and systemic arterial pressures and heart rate during preload reduction with 0.5 mg nitroglycerin sublingually. Basal plasma ANF levels were higher in patients with congestive heart failure compared to normal controls, and correlated to right atrial, pulmonary arterial, and pulmonary capillary wedge pressures. After nitroglycerin all patients had reductions in right atrial, pulmonary arterial, and pulmonary capillary wedge pressures and a simultaneous decrease in plasma ANF concentrations, reaching lowest values after 10 min. Central pressures and plasma ANF rose to baseline values within 30 min. After nitroglycerin plasma ANF concentrations correlated to pulmonary arterial and pulmonary capillary wedge pressures, while changes in plasma ANF correlated to changes in right atrial and pulmonary arterial pressures. These results provide further evidence that ANF is released by a pressure-sensitive mechanism and demonstrates that ANF secretion in relation to central pressure variations is preserved in patients with congestive heart failure and that the response is rapid.     

Effects of dobutamine and salbutamol on haemodynamics and atrial natriuretic factor in patients with severe congestive heart failure.

The influence of two cardiac inotropic drugs, dobutamine and salbutamol, on plasma atrial natriuretic factor (ANF) was investigated in 20 patients with congestive heart failure. All were in New York Heart Association class-III or IV. The patients underwent right heart catheterization with determination of central pressures, cardiac output, and pulmonary arterial plasma ANF during incremental infusions with dobutamine or salbutamol. Fourteen patients completed the study. Both drugs induced comparable increases in cardiac index and decreases in total systemic vascular resistance (P less than 0.01) without significant changes in central pressures. Heart rate rose after salbutamol (P less than 0.05), but not after dobutamine. No changes in plasma ANF were observed after either of the drug infusions. ANF secretion rate was calculated from simultaneous measurements of ANF in right atrial and pulmonary arterial plasma before and after salbutamol infusion, and median values rose more than seven-fold (P less than 0.05). The results demonstrate that ANF secretion rate is augmented after beta-adrenergic agents, possibly by a direct beta 2-adrenergic stimulation, in patients with severe congestive heart failure, and that changes in plasma ANF are an insufficient measure of ANF release when patient samples are small.     

Plasma atrial natriuretic factor in low output heart failure syndromes

Summary Plasma atrial natriuretic factor, aldosterone, renin activity, and antidiuretic hormone were studied in low output heart failure syndromes: cardiogenic shock in ten patients with acute myocardial infarction of the anterior wall (first group), hypovolemic shock after melena from peptic ulcer in ten subjects (second group), and hypotension with bradycardia syndrome in ten patients with acute myocardial infarction of the inferior wall (third group). Circulating atrial natriuretic factor in patients with cardiogenic shock (102.4±7.4 pg/ml) was significantly higher than in healthy volunteers matched for sex and age (8.4±0.3 pg/ml). In these patients there was a positive correlation between atrial natriuretic factor and central venous pressure values. Atrial natriuretic factor and central venous pressure values in the second and third groups were within normal range. Plasma aldosterone was high in all groups, plasma renin activity was elevated in the first and third groups, and high antidiuretic hormone was observed in the first and second groups. These findings indicate that in low output heart failure syndromes only hemodynamic changes affecting the atria stimulate atrial natriuretic factor release. No correlations were found between plasma atrial natriuretic factor and other hormones. In particular, high atrial natriuretic factor levels in the patients with cardiogenic shock did not inhibit release of aldosterone, renin, or antidiuretic hormone. It may be surmised that in these patients the hemodynamic effects override the inhibitory effects of atrial natriuretic factor.Abbreviations ANF atrial natriuretic factor - ANP atrial natriuretic peptide - ANOVA analysis of variance - ACTH adrenocorticotropin hormone     

Atrial natriuretic peptide during head-up tilt induced hypovolaemic shock in man

To evaluate the importance of right atrial filling pressure versus central blood volume for the plasma concentration of atrial natriuretic peptide in man, head-up tilt to 50 degrees maintained until the appearance of presyncopal symptoms was carried out in six healthy males. Head-up tilt increased thoracic electrical impedance from 35.4 +/- 0.9 (mean and SE) to 39.2 +/- 0.9 ohm, mean arterial pressure from 64.5 +/- 3.6 to 76.6 +/- 3.0 mmHg and heart rate from 51 +/- 3 to 85 +/- 4 beats min-1 (P less than 0.01). After 35 +/- 7 min presyncopal symptoms appeared, together with a decrease in mean arterial pressure to 51 +/- 4 mmHg and in heart rate to 59 +/- 7 beats min-1 (P less than 0.01). Central venous pressure (2.1 +/- 1.0 mmHg) did not change significantly, but atrial natriuretic peptide decreased from 9.4 +/- 1.6 to 4.2 +/- 1.3 pmol l-1 (P less than 0.01) and was inversely related to thoracic impedance (r = -0.65, n = 44, P less than 0.001). The results indicate that changes in the central blood volume rather than in central venous pressure determine the secretion of atrial natriuretic peptide in man.     

Plasma levels of atrial natriuretic peptide at rest and during exercise in heart failure--influence of cardiac rhythm and haemodynamics.

The relationship between plasma levels of immunoreactive atrial natriuretic peptide (ir-ANP), arginine vasopressin (AVP), cardiac rhythm and different haemodynamic variables were studied at rest and during exercise in 16 patients with heart failure undergoing heart catheterization for clinically indicated reasons. Even though there was no significant relationship between pulmonary capillary wedge pressure (PCW) and ir-ANP at rest (r = 0.39; P = 0.14) changes in these variables with exercise correlated well (r = 0.71; P = 0.002). Change in right atrial mean pressure, heart rate, mean arterial blood pressure or cardiac index did not significantly influence change in plasma levels of ir-ANP. The correlation between PCW and AVP at rest (r = 0.92; P less than 0.001) disappeared during exercise. Calculated ir-ANP/PCW ratios decreased slightly during exercise, but were not influenced by initial atrial pressures or atrial fibrillation. These observations provide evidence for a similar responsiveness of ANP in patients with sinus rhythm and atrial fibrillation. The ability of rapid change in ANP plasma levels during exercise was preserved and proportional to changes in PCW over a wide pressure range in the studied patient group. This finding indicates that left atrium distension rather than right atrium distension is the major determinant for the release of ANP in patients with congestive heart failure. The observed rapid responsiveness of ANP to change in left atrial pressure may allow the hormone to modulate haemodynamic response during short periods of exercise.     

Computer simulation of haemodynamic parameters changes with left ventricle assist device and mechanical ventilation

Left Ventricular Assist Device is used for recovery in patients with heart failure and is supposed to increase total cardiac output, systemic arterial pressure and to decrease left atrial pressure. Aim of our computer simulation was to assess the influence of Left Ventricular Assist Device (LVAD) on chosen haemodynamic parameters in the presence of ventilatory support. The software package used for this simulation reproduces, in stationary conditions, the heart and the circulatory system in terms of pressure and volume relationships. Different circulatory sections (left and right heart, systemic and pulmonary arterial circulation, systemic and pulmonary venous circulation) are described by lumped parameter models. Mechanical properties of each section are modelled by RLC elements. The model chosen for the representation of the Starling's law of the heart for each ventricle is based on the variable elastance model. The LVAD model is inserted between the left atrium and the aorta. The contractility of the heart and systemic arterial resistance were adjusted to model pathological states. Our simulation showed that positive thoracic pressure generated by mechanical ventilation of the lungs dramatically changes left atrial and pulmonary arterial pressures and should be considered when assessing LVAD effectiveness. Pathological changes of systemic arterial resistance may have a considerable effect on these parameters, especially when LVAD is applied simultaneously with mechanical ventilation. Cardiac output, systemic arterial and right atrial pressures are less affected by changes of thoracic pressure in cases of heart pathology.     

Atrial natriuretic factor secretion: a role for atrial systolic ejection force?

The increase in plasma concentration of atrial natriuretic factor in heart transplant patients has not been fully elucidated. Besides an eventual pressure or volume overload leading to passive atrial distension, the atrial tension developed during atrial systole, or atrial ejection force, which may be increased by the transplantation procedure, is an important determinant of atrial natriuretic factor release. We therefore determined the plasma concentration of atrial natriuretic factor and the maximal atrial ejection force in 15 heart transplant patients and 8 controls, matched for age and body mass. Atrial ejection force, as defined as the force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, was obtained using combined two-dimensional imaging and doppler echocardiography. Serum creatinin concentrations, heart rate [91.9 (SD 13.2) vs 71.8 (SD 10.9) beats · min^–1], mean arterial blood pressure [103.9 (SD 9.8) vs 87.4 (SD 5.8) mmHg, 13.85 (SD 1.31) vs 11.65 (SD 0.77) kPa], left ventricular posterior wall thickness and interventricular septum thickness were higher in heart transplant patients compared to controls. Plasma concentration of atrial natriuretic factor was also elevated in heart transplant patients [63.9 (SD 18.1) vs 34.0 (SD 3.2) pg · ml^–1; P<0.001]. In contrast, although the left atrial area was greater in heart transplant patients [28.2 (SD 4.8) vs 15.8 (SD 2.5) cm²; P<0.001], mitral area, transmitral Doppler A-wave maximal velocity and atrial ejection force were similar in transplant and in control patients [7.7 (SD 3.5) vs 8.9 (SD 2.8) kdyn, 77 (SD 35) vs 89 (SD 28) mN]. No significant correlation was observed between concentration of atrial natriuretic factor and atrial ejection force, either in heart transplant patients or in controls. Thus, the elevated plasma concentration of atrial natriuretic factor observed in these heart transplant patients was multifactorial in origin, and was considered to depend upon an hypersecretion rather than upon a decreased clearance rate. Moreover, it is suggested that the atrial ejection force was unlikely to have participated in this enhanced release of atrial natriuretic factor.     

Cardiac natriuretic peptide hormones during artificial cardiac pacemaker stimulation and left heart catheterization

Summary Brain natriuretic peptide (BNP) is synthesized and released predominantly in the ventricular myocardium whereas atrial natriuretic peptide (ANP) is produced mainly in the atria. This study evaluated whether artificial pacemaker stimulation or left heart catheterization results in specific changes in BNP and ANP plasma levels. Both BNP and ANP responded sensitively to changes in pacemaker stimulation (single-chamber pacemakers; pacing rates of 72 and 92/min) and during the left heart catheterization procedure. However, whereas higher pacing resulted in a more pronounced increase in plasma BNP levels, a stronger ANP release followed catheterization. This incongruous rise in ANP and BNP plasma concentrations points to at least partly independent mechanisms govering the release of BNP and ANP.Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide     

Differentiation of the peptidergic vasoregulatory response to standardized splanchnic hypoperfusion by acute hypovolaemia or sepsis in anaesthetized pigs.

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug     

ANF-Konzentrationen und Drücke im kleinen Kreislauf unter Belastung vor und nach Koronardilatation

Summary According to several reports of close correlations between pulmonary artery pressure and ANF plasma levels it would be convenient to replace invasive pressure monitoring by ANF determination.Mean pulmonary artery and right atrial pressures and pulmonary artery as well as peripheral venous ANF plasma concentrations were measured in 24 patients before and after coronary angioplasty (PTCA) continuously at rest and during exercise: At rest, both pressure and ANF-values remained unchanged before and after PTCA. At exercise, there was a decrease of mean pulmonary artery pressure (from 41.3±8.6 to 31.5±7.4 mmHg,p<0.001), mean right atrial pressure (from 11.9±3.0 to 9.0±2.3 mmHg,p< 0.001), pulmonary artery (282.5±191.0 to 207.3±157.2 pg/ml,p<0.05) and peripheral venous (112.7±48.0 to 97.1±53.2 pg/ml, n.s.) ANF concentration after PTCA. We found no correlation between PTCA-induced changes of right arterial pressures and ANF concentrations, while changes of pulmonary artery pressures were significantly correlated to changes of peripheral venous (r=0.79,p<0.001) as well as pulmonary artery (r=0.59,p<0.01) ANF concentrations at exercise. In 6 of the 24 patients, however there was an inverse relationship between changes of pulmonary artery pressures and ANF concentrations. — Our data demonstrate a significant correlation between changes of ANF plasma level and pulmonary artery pressure values at exercise after PTCA. In the individual case however invasive pressure monitoring cannot be replaced by determination of ANF plasma levels.

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Abkürzungsverzeichnis ANF Atrialer natriuretischer Faktor - PTCA Perkutane transluminale Koronarangioplastie - PPa mittlerer pulmonalarterieller Druck - PPc mittlerer pulmonalcapillärer Druck - PRA mittlerer rechtsatrialer Druck Herrn Prof. Dr. med F. Scheler zum 65. Geburtstag gewidmet     

Differentiation of the peptidergic vasoregulatory response to standardized splanchnic hypoperfusion by acute hypovolaemia or sepsis in anaesthetized pigs

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.     

Role of atrial natriuretic peptide in the development of arterial hypertension in patients with pubertal hypothalamic syndrome

The role of a depressor factor, atrial natriuretic peptide, in the development of arterial hypertension in adolescents with pubertal hypothalamic syndrome was studied in 52 patients and 13 healthy males aged 13–24 years. The duration of disease was 2–11 years. Radioimmunological methods were used to measure plasma atrial natriuretic peptide, plasma renin activity, and serum aldosterone. Patients with borderline arterial hypertension were found to have a significant reduction in their atrial natriuretic peptide levels, and this correlated directly with the renin-aldosterone system, demonstrating insufficiency of the depressor system in patients with pubertal hypothalamic syndrome and the involvement of atrial natriuretic peptide in the development of arterial hypertension, along with disturbances in the functional relationship between atrial natriuretic peptide and the renin-aldosterone system. This article was presented at the III All-Russian Congress of Endocrinologists. Samara Medical University. Translated from Problemy éndokrinologii, Vol. 43, No. 4, pp. 21–22, July–August, 1997.     

Increase in atrial pressure releases atrial natriuretic peptide from isolated perfused rat hearts

To elucidate the mechanism involved in the release of atrial natriuretic peptide, we modified the isolated perfused rat heart preparation to permit a step-wise increase in right atrial tension. Perfusate was introduced into the right atrium through the superior vena cava and was collected via the pulmonary artery. Right atrial pressure was manipulated by changing the perfusion rate. Perfusate from the pulmonary artery was collected in 1-min-fractions, extracted, and assayed for atrial natriuretic peptide like immunoreactivity (ANP-li). The basal rate of ANP-li release at an atrial pressure of 1.41±0.31 mm Hg was 964±144 pg/min (n=11). As right atrial pressure was increased (range 0.4–4.5 mm Hg), a linear correlation (r=0.85,P<0.001) was observed between the change in ANP-li release and the change in atrial pressure. High pressure liquid chromatography revealed that the major fraction in the perfusate had the same elution time than alpha-rANP. This peak fraction, as well as synthetic atriopeptin III, caused a dose-dependent relaxation in rat aortic strips that had been subjected to contraction with norepinephrine. Further, it corresponded exactly to the material we previously identified in rat plasma. These results suggest that atrial distension is involved in the release of ANP. In addition, ANP is released per se, as the active peptide.     

Atrial-specific granule number and plasma atrial natriuretic peptide in rats: effects of beta-adrenoceptor blockade and sodium intake

An interrelationship between atrial natriuretic peptide (ANP) and the renin-angiotensin system has been established. Both of these hormonal systems are modulated by sodium balance. The role of the beta-adrenoceptor in the regulation of release of ANP is not clear. We therefore undertook a study to examine changes in atrial-specific granule number and plasma ANP level following beta-adrenoceptor blockade in rats on low and high sodium intakes. A low-sodium diet, as compared with a high-sodium diet, elevated right and left atrial-specific granule number (right atria 54.6 +/- 8.7 vs. 42.3 +/- 5.7; left atria 47.7 +/- 7.7 vs. 30.6 +/- 3.4 granules/unit area) and plasma renin activity (28 +/- 3.7 vs. 5.4 +/- 0.8 ng AI/ml/hr). Plasma ANP levels were lower in the low-sodium animals (98 +/- 34 vs. 345 +/- 38 pg/ml). When treated with the nonspecific beta-adrenoceptor blocker propranolol, the elevated plasma renin activity and atrial-specific granule number in rats on a low sodium intake were significantly less. Neither of these parameters changed in rats on a high sodium intake. Conversely, propranolol treatment resulted in lower plasma ANP levels in rats with high sodium intake. The already-suppressed plasma ANP level in rats on a low-sodium diet was unaltered with beta-adrenoceptor blockade. The results suggest that dietary sodium intake is an important determinant of the response of atrial-specific granule number and plasma ANP levels following beta-adrenoceptor blockade with propranolol.     

Atrial natriuratic peptide and experimental vasorenal hypertension in rats

Vasorenal hypertension in rats resulted in increase of arterial pressure, the plasma concentration of creatinine and potassium. By EM immunocytochemistry we have demonstrated that atrial natriuretic peptide (ANP) was kept in the granules of secretory cardiomyocytes of the right atrium. It has shown that cardiomyocytes released ANP by means of diffusion. The increased secretion of atrial natriuretic peptide has been detected in blood. However the physiological effects this peptide probably was impaired due to the reducing of the density of natriuretic peptide receptors.     

Atrial natriuretic factor and central venous pressure during intermittent and continuous lower-body positive pressure in healthy humans

In eight healthy volunteers undergoing 16 experiments in a cross-over design central venous pressure (CVP) and atrial natriuretic factor (ANF) in central venous plasma were measured during a 30 min control period followed by three separated periods of 10 min lower-body positive pressure (LBPP) or 90 min continuous LBPP induced by inflation of a military anti-G suit to evaluate the effect of short repeated and of extended increases in right atrial pressure on plasma ANF levels. CVP increased significantly during each of three separate periods of intermittent LBPP, and 15 min after application of continuous LBPP (P less than 0.025 for all). Blood pressure and heart rate did not change. During intermittent LBPP plasma ANF levels increased 10 min after the first inflation of the MAGT-suit (P = 0.013), but not after the second or third inflation. During continuous LBPP plasma ANF remained unchanged until 90 min after application of LBPP where a significant rise was observed (P = 0.023). The data demonstrate that the ANF response to short-term increases in right atrial pressure, as small as 2.5 mmHg, is maximal within 10 min and that repeated pressure stimuli may decrease ANF release. Sustained increases in right atrial pressure are not associated with increases in plasma ANF until long after initiation of the pressure stimulus suggesting rapid receptor-binding of ANF and that the ANF receptors might be saturated during continuously elevated ANF levels.     

Plasma ANP during hypertonic NaCl infusion in man

To determine the relationship between hyperosmolality and immunoreactive atrial natriuretic peptide of heart atrial plasma six healthy men were given 0.06 ml kg^-1 min^-1 855 mmol 1^-1 NaCI, i.v., for 2 h. The right atrial pressure and atrial plasma atrial natriuretic peptide were measured. During the infusion, right atrial pressure was kept constant by lowering the legs of the subject in a supine position downwards if any increase in the pressure was seen. There was a significant and linear increase in atrial serum osmolality, from 288 ± 3.3 to 307 ± 3.2mOsm kg^-l (P < 0.001). No statistically significant changes in right atrial pressure were seen. Regression analysis revealed that there was a statistically significant correlation between serum osmolality and plasma ANP in three subjects (responders) (r²: 0.5 241 , 0.8 965 , 0.6695). In three other subjects (nonresponders), there was no correlation between osmolality and ANP. The mean basal osmolality of responders was 280 mOsm kg^-1 and the mean basal osmolality of nonresponders was 295 mOsm kg^-1. In contrast, all subjects responded with an increase in plasma ANP (P < 0.05) after RAP had been increased by tilting the legs of the subject upwards for 30 min. We conclude that the right atrial pressure regulates the release of atrial natriuretic peptide. Serum hyperosmolality may also contribute to the the regulation of atrial natriuretic peptide independently of the right atrial pressure in man.     

Effects of salt loading on the fractional volume of atria-specific granules in Dahl salt-sensitive and salt-resistant rats

The cardiac atria are known to play a role in blood volume homeostasis, secreting a peptide that induces a potent natriuresis and diuresis. This peptide is atrial natriuretic factor (ANF), and its primary site of storage is within atria-specific granules found in atrial cardiocytes. Since salt loading results in an increase in circulating levels of ANF, our aim was to determine if the atria-specific granule population in the cardiocytes of Dahl rats would decrease accordingly. To this end, the fractional volume of the atria-specific granules was determined by ultrastructural morphometric analysis in the Dahl salt model of hypertension. This analysis was performed on the right atria of Dahl Salt-resistant (DR) and salt-sensitive (DS) rats fed either a low-salt (0.4%) or high-salt (8%) diet for 12 weeks prior to sacrifice. DR and DS rats fed a low-salt diet had significantly reduced plasma sodium levels and osmolalities, and a significantly lower mean arterial blood pressure than did rats fed a high-salt diet. The fractional volume of atria-specific granules was significantly lower in salt-loaded DR (P less than 0.01) and DS (P less than 0.025) rats than in their respective low-salt controls. This significant decrease in atrial granules corresponds to the reported decrease in the storage of atrial ANF in salt-loaded rats, and provides a morphological verification of the biochemical studies. Moreover, these results, in combination with a growing body of physiological data, lend support to the hypothesized role of ANF in the regulation of water-electrolyte balance, which may play an important role in cardiovascular pathophysiological states related to hypertension.     

Atrial natriuretic peptide during acute treatment of congestive heart failure

Atrial natriuretic peptide (ANP) induces potent diuretic/natriuretic, vasorelaxing and aldosterone inhibitory effects. Increased plasma levels in congestive heart failure (CHF) have been reported. The aim of this study was to investigate plasma immunoreactive ANP (ir-ANP) levels during acute treatment of CHF. Seven patients with CHF underwent cardiac catheterization. Ir-ANP plasma levels were followed up to two h after administration of an orally given phosphodiesterase inhibitor (Milrinone); a substance with positive inotropic and peripheral vasodilating properties. In all patients cardiac output increased and cardiac filling pressures decreased markedly. Initially high ir-ANP plasma levels decreased. Our patients did not have an increased blood volume. It is concluded that plasma ir-ANP levels in the pulmonary artery rapidly decrease when atrial pressure is reduced. These data suggest that atrial pressure is the major determinant for release of ir-ANP in man and that the ability to respond quickly to changes in cardiac filling pressures is maintained in patients with severe CHF. Plasma ir-ANP levels may also become useful as an index of the degree of heart failure and serve as a tool in monitoring response to drug therapy.