Plasma Atrial Natriuretic Polypeptide Research Articles

Plasma Atrial Natriuretic Polypeptide and Angiotensin II in Rats during Anesthesia and Volume Loading

These experiments investigated the effect of halothane or fentanyl anesthesia on plasma atrial natriuretic polypeptide (ANP) and angiotensin II (AII) concentrations and the response to a 30% blood volume load in rats. Halothane (1.1% and 2.2% inspired) or fentanyl (50 and 200 micrograms/kg) anesthesia alone produced little change in basal plasma ANP levels but did increase plasma AII levels above unanesthetized baseline concentrations. A 30% blood volume load in conscious rats produced a transient increase in blood pressure and central venous pressure, a threefold rise in plasma ANP, and a decrease in AII. These effects were not significantly altered by fentanyl anesthesia. In contrast, during 2.2% halothane anesthesia the increase in plasma ANP produced by volume loading was greater and the decrease in AII was abolished. These results indicate that fentanyl does not increase basal ANP levels or markedly change the hormonal response to a volume load. Altered responses seen during deep halothane anesthesia may result from cardiovascular changes or a direct stimulation of physiological mechanisms that release ANP.

Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.

To determine whether pharmacological control of blood pressure could affect the renal function and levels of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) with renal ablation, and to ascertain the benefits of antihypertensive drugs, we studied effects of oral administration of captopril (50 mg/kg/day), an inhibitor of angiotensin converting enzyme, benidipine (3 mg/kg/day) and nilvadipine (10 mg/kg/day), newly developed blockers of calcium channel, and indapamide (10 mg/kg/day) for 14 days on systolic blood pressure, serum creatinine, blood urea nitrogen, and plasma ANP concentration in SHR subjected to surgical removal of the left kidney and infarction of two-thirds of the right kidney (5/6 nephrectomy) a week before. Three weeks after the surgery, systolic blood pressure (mmHg) in the untreated group was 253 +/- 9 (n = 10), in the captopril group 156 +/- 9 (n = 7, p less than 0.05), in the benidipine group 197 +/- 9 (n = 7, p less than 0.05), in the nilvadipine group 146 +/- 9 (n = 7, p less than 0.05) and in the indapamide group 206 +/- 5 (n = 7, p less than 0.05). Serum creatinine (mg/100 ml) was lower in the captopril group (0.58 +/- 0.02, n = 7, p less than 0.05) and in the benidipine group (0.50 +/- 0.03, n = 7, p less than 0.05) but not in the nilvadipine group and in the indapamide group 3 weeks after 5/6 nephrectomy compared to the untreated group. Blood urea nitrogen was also lower in the captopril group and in the benidipine group but not in the nilvadipine group and in the indapamide group. Plasma ANP concentration was significantly reduced by the treatment with captopril and benidipine but not with nilvadipine and indapamide. These results suggest that the reduction of blood pressure by the inhibition of angiotensin converting enzyme with captopril has the potential to ameliorate renal function of the SHR with remnant kidney, a model of chronic renal failure with hypertension, associated with the decreased concentration of plasma ANP. However, it remains to be determined whether the reduction of blood pressure by calcium channel blockers may be involved in the delayed progression of renal failure in this model since there were disparate effects on renal function and plasma ANP concentration with these two calcium channel blockers.

ＳＩＡＤＨを合併した上顎癌頭蓋内浸潤例

We encountered a case of maxillary carcinoma with intracranial invasion complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) which occurred following carbamazepine administration for meningitis. A 55-year-old female with maxillary carcinoma with intracranial invasion had been treated for increased intracranial pressure by steroids and glycerol. The antidiuretic hormone level was not suppressed by hypoosmolality of the plasma and alpha-human atrial natriuretic poly-peptide was within the normal range. She did not regain consciousness and died of cachexia four months later.

Increased secretion of atrial natriuretic polypeptide in response to cardiac pacing.

Effects of cardiac pacing on secretion of atrial natriuretic polypeptide (ANP) were examined in 20 patients during cardiac catheterization under control conditions. The plasma ANP concentration in the coronary sinus (900 +/- 115 pg/ml) was significantly higher than those in the aorta (147 +/- 19 pg/ml) and the femoral vein (105 +/- 15 pg/ml) (p less than 0.001). The plasma ANP concentration was also significantly higher in the aorta than in the femoral vein (p less than 0.001). Its concentration at all three sites significantly increased during cardiac pacing (from 900 +/- 115 to 1461 +/- 218, from 147 +/- 19 to 250 +/- 36, and from 105 +/- 15 to 150 +/- 24 pg/ml, respectively). However, mean right atrial pressure and mean pulmonary capillary wedge pressure showed no significant changes between control conditions and during pacing (5 +/- 1 vs 6 +/- 1, and 8 +/- 1 vs 8 +/- 1 mmHg). Furthermore, there was no significant correlation between ANP secretion and the pressure in both atria. Thus, cardiac pacing can release ANP from the heart without increasing atrial pressure.

Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy.

To examine whether atrial natriuretic polypeptide (ANP) is released from the left ventricle in patients with dilated cardiomyopathy (DCM) we measured plasma ANP level in the aortic root (Ao), the anterior interventricular vein (AIV), the great cardiac vein (GCV), and the coronary sinus (CS) in 11 patients with DCM and 18 control subjects. Plasma ANP levels in Ao, AIV, GCV, and CS were 454 +/- 360, 915 +/- 584, 1,308 +/- 926, and 1,884 +/- 1,194 pg/ml, respectively, in the patients with DCM and 108 +/- 42, 127 +/- 55, 461 +/- 224, and 682 +/- 341 pg/ml, respectively, in the control subjects. There was no significant difference in the plasma ANP levels between Ao and AIV in the control subjects. On the contrary, there was a significant (P less than 0.001) step-up in plasma ANP levels between Ao and AIV in patients with DCM. Thus, the difference in ANP levels between Ao and AIV was significantly increased in patients with DCM as compared with the control subjects (461 +/- 248 vs. 19 +/- 59 pg/ml, P less than 0.001). The difference in ANP levels between Ao and CS was also significantly increased in patients with DCM as compared with the control subjects (1,429 +/- 890 vs. 577 +/- 318 pg/ml, P less than 0.001). We conclude that ANP is released in increased amounts into the circulation from the left ventricle as well as from the heart as a whole in patients with DCM.

Effects of hypercalcemia and ouabain on plasma atrial natriuretic polypeptide in anesthetized dogs.

For the purpose of examining the role of calcium ion in the secretory process of atrial natriuretic polypeptide (ANP), we studied the effects of hypercalcemia and ouabain on plasma concentration of immunoreactive ANP (irANP). Pentobarbital sodium-anesthetized dogs were treated with calcium chloride infusion (0.136 mmol.kg-1.min-1, 10 min) or ouabain injection (30 micrograms/kg), and plasma irANP concentration, right atrial pressure, mean arterial pressure, heart rate, and serum calcium concentration were measured. To evaluate the effect of rising arterial pressure, plasma irANP concentration was also measured in dogs treated with phenylephrine hydrochloride (10 micrograms/kg). With calcium chloride infusion, serum calcium concentration and plasma irANP concentration, respectively, increased to about three times and about four times their basal levels. This increase of plasma irANP concentration was not attenuated by pretreatment with adrenoceptor blockers. Ouabain increased plasma irANP concentration to approximately 2.5 times the initial level. Neither calcium chloride nor ouabain produced any effect on right atrial pressure and heart rate, but both significantly increased mean atrial pressure. Phenylephrine caused a greater increase in mean arterial pressure than both calcium chloride and ouabain. However, there was no significant increase in plasma irANP concentration. These results suggest that the calcium ion may play a key role in the secretory process of ANP.

Exaggerated secretion of atrial natriuretic polypeptide during dynamic exercise in patients with essential hypertension

The plasma concentration of atrial natriuretic polypeptide (ANP) was measured in nine patients with essential hypertension during two grades of exercise tests performed in the supine position on a bicycle ergometer. The plasma ANP concentration significantly increased from 97.0 ± 19.2 pg/ml to 107.6 ± 23.7 pg/ml ( p < 0.05) during low-grade exercise (50% of the maximal heart rate) and from 96.2 ± 16.5 pg to 192.8 ± 30.7 pg/ml ( p < 0.01) during high-grade exercise (75% of the maximal heart rate). During high-grade exercise plasma epinephrine and norepinephrine concentrations showed significant increases. The plasma ANP concentration was significantly correlated with systolic blood pressure ( r = 0.51; p < 0.05). Patients with essential hypertension showed greater absolute increases in the plasma ANP concentration and systolic blood pressure during exercise compared to normotensive subjects. These results suggest that exercise stimulates secretion of ANP in response to its intensity in patients with essential hypertension and that a greater rise in atrial pressure, resulting from a greater elevation of systolic blood pressure, may be involved in the exaggerated secretion of ANP in patients with essential hypertension.

Sodium balance effects on renin, angiotensinogen, and atrial natriuretic polypeptide mRNA levels.

The expressions of the renin, angiotensinogen, and atrial natriuretic polypeptide (ANP) genes were studied in rats with varying sodium intakes. mRNAs for angiotensinogen and renin were measured by a sensitive radiodensitometric hybridization assay. ANP mRNA was determined by a dot-blot hybridization assay. In the high-sodium state, plasma renin concentration (PRC), renal renin concentration (RRC), and renal renin mRNA decreased by 88, 90, and 75%, respectively. In the low-sodium state, PRC, RRC, and renin mRNA increased 17-fold, 2.5-fold, and 4.5-fold, respectively. With captopril treatment during sodium depletion, PRC and renin mRNA increased 144-fold and 17.1-fold, respectively, and RRC increased 4.2-fold. The angiotensinogen mRNA level in the liver and kidney decreased in the high-sodium and increased in the low-sodium state to similar extents. Captopril treatment decreased angiotensinogen mRNA in both organs by about half. Plasma ANP and ANP mRNA decreased in the low- compared with the high-sodium state, whereas atrial ANP content was unaltered in both low- and high-sodium states. These results demonstrate that sodium intake affects the expression of the renin and angiotensinogen genes and slightly alters the expression of ANP gene.

Increased Synthesis and Secretion of Atrial Natriuretic Polypeptide During Viral Myocarditis

To elucidate the pathophysiological role of atrial natriuretic polypeptide (ANP) in diseased hearts, ANP levels in atrial and ventricular tissues and plasma were investigated in mice with congestive heart failure after viral myocarditis. The study was performed on day 14 after encephalomyocarditis viral inoculation, when congestive heart failure developed. The atrial ANP level increased to a value two times higher than that of noninoculated age-matched mice (the control mice). The ventricles of the control mice contained an approximately 1,000-fold lower ANP level than the atrial ANP level. The ventricular ANP concentration of the infected mice showed about a 21 times higher level than the control value. The plasma ANP level was also elevated 20 times. On immunofluorescence studies, increase of immunostaining were found in the atrial of the infected mice, and positive staining appeared on the cardiocytes in almost all areas of the remaining ventricular tissues of the infected mice, whereas staining was not found on the ventricles of the control mice. The staining seemed particularly strong in the area surrounding the myocardial lesions. These results indicate that atrial and ventricular ANP synthesis and ANP secretion increase in the heart with viral myocarditis. The marked increase in the ventricular ANP level suggests that the ventricle is another important production site for circulating ANP.

Effect of rapid sodium load on circulating atrial natriuretic polypeptide.

The hypothesis that an increase in plasma sodium concentration (PNa) causes an increase in circulating atrial natriuretic polypeptide (ANP) was examined in conscious dogs. NaCl solution in small volume (0.3 ml/kg body wt) and at high concentration (20%) was injected intravenously within 2 s to rapidly increase PNa. PNa rapidly increased to 5.1 +/- 0.3 meq/l. Urinary excretion of sodium and water increased to 4.1 and 2.5 times the control levels, respectively. Plasma vasopressin level increased to 3.7 times the control level. Plasma ANP level (PANP) did not change significantly. PANP corrected for sodium-induced hemodilution did not change either. On a different day, a double amount of sodium (0.6 ml/kg body wt of 20% NaCl solution) was intravenously injected into the dogs. PNa increased by 7.3 +/- 0.4 meq/l, which was significantly more than the increase after the 0.3 ml/kg injection. PANP with or without correction for hemodilution again did not change. These results indicate that a rapid increase in PNa within the physiological range does not cause elevation of circulating ANP. This suggests that ANP does not contribute to the regulation of plasma sodium concentration.

Central interaction of the brain atrial natriuretic polypeptide (ANP) system and the brain renin-angiotensin system in ANP secretion from heart--evidence for possible brain-heart axis.

To elucidate the involvement of the brain renin-angiotensin system and the brain atrial natriuretic polypeptide (ANP) system in the regulation of ANP secretion from the heart, the effects of intracerebroventricular administration of angiotensin II and ANP on the plasma ANP level were examined in conscious unrestrained rats. The intracerebroventricular administration of angiotensin II at doses of 100 ng and 1 microgram significantly enhanced ANP secretion induced by volume-loading with 3-mL saline infusion (peak values of the plasma ANP level: control, 220 +/- 57 pg/mL; 100 ng angiotensin II, 1110 +/- 320 pg/mL, p less than 0.01; 1 microgram angiotensin II, 1055 +/- 60 pg/mL, p less than 0.01). The intracerebroventricular injection of angiotensin II at the same doses alone had no significant effect on the basal plasma ANP level. The enhancing effect of central angiotensin II on ANP secretion induced by volume-loading was significantly attenuated by pretreatment with the intravenous administration of the V1-receptor antagonist of vasopressin or with the intracerebroventricular administration of phentolamine. The intracerebroventricular administration of alpha-rANP(4-28) (5 micrograms) had no significant influence on the basal plasma ANP level; however, it significantly attenuated central angiotensin II potentiating effect of volume-loading induced ANP secretion. These results indicate that the brain renin-angiotensin system regulates ANP secretion via the stimulation of vasopressin secretion and (or) via the activation of the central alpha-adrenergic neural pathway, and that the brain ANP system interacts with the brain renin-angiotensin system in the central modulation of ANP secretion from the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological factors of atrial natriuretic polypeptide release and its neural regulation in conscious dogs.

We have examined physiological factors in atrial natriuretic polypeptide (ANP) release and whether or not the cardiac nerves control release of ANP. Two possible factors were tested, an increase in plasma sodium level (PNa) and an increase in atrial pressure. Injection of 1.0 or 2.0 mEq/kg of sodium ions elevated PNa by 5.3 +/- 0.3 or 7.3 +/- 0.4 mEq/L, respectively, but plasma ANP level (PANP) did not change. Infusion of 18 ml/kg of 3% Dextran-40 over 5 min increased mean left atrial pressure (MLAP) by 7.6 +/- 0.9 mmHg. PANP increased from 206 +/- 17 pg/ml to 260 +/- 25 pg/ml, which was not significant. PANP, corrected for hemodilution, significantly increased to 348 +/- 34 pg/ml. These results suggest that PNa increase does not promote ANP release, but that an atrial pressure increase does. This transient volume load did not induce full response of the ANP releasing system. A prolonged volume load for 45 min increased corrected PANP to 435 +/- 73 pg/ml. A close linear correlation was found between the increases in MLAP and PANP. These facts indicate that prolonged volume expansion is necessary to induce full response of the ANP releasing system. Complete cardiac denervation did not affect the tonic level of plasma ANP, volume expansion-induced increase in PANP, or the sensitivity of the ANP releasing system. Thus we conclude that the cardiac nerves do not control ANP release caused by volume expansion.

Simultaneous measurement of atrial natriuretic polypeptide (ANP) messenger RNA and ANP in rat heart — Evidence for a preferentially increased synthesis and secretion of ANP in left atrium of spontaneously hypertensive rats (SHR) —

Tissue levels of atrial natriuretic polypeptide (ANP) messenger RNA (ANPmRNA) and ANP in the rat heart were measured simultaneously. In Wistar rats, ANPmRNA of the same size (approximately 0.95 kbp) was detected in all four chambers of the rat heart. The ANPmRNA level was the highest in the right atrium, and the left atrial level was slightly lower than the right atrial level. Ventricular levels were more than two orders of magnitude lower than atrial levels. Tissue ANP concentrations of four chambers were roughly parallel to ANPmRNA levels. In spontaneously hypertensive rats (SHR) with the elevated plasma ANP level, the ANPmRNA level in the left atrium was substantially increased. The left/right ratio of atrial ANPmRNA level in SHR (150%) was higher than that in control Wistar Kyoto rats (WKY) (90%). In contrast, the left/right ratio of atrial ANP concentration was decreased in SHR (44%) compared with that in WKY (84%). The ratio of ANP to ANPmRNA levels in the left atrium of SHR was about three times smaller than that in the right atrium of SHR, and those in bilateral atria of WKY. These results indicate that the biosynthesis and secretion of ANP from the left atrium is preferentially increased in SHR. Thus, simultaneous determination of ANPmRNA and ANP levels is a refined strategy of investigation for the biosynthesis, storage and secretion of ANP.

Relationship between plasma atrial natriuretic polypeptide concentration and hemodynamic measurements in children with congenital heart diseases

The plasma alpha-atrial natriuretic polypeptide (alpha-ANP) concentration in the peripheral veins of children with congenital heart diseases was measured by radioimmunoassay and compared with cardiac catheterization data. Every patient with heart failure had a higher alpha-ANP concentration (132.1 to 858.7 pg/mL) than the upper limit of the normal range (11.7 to 98.7 pg/mL), whereas more than half of the patients without heart failure had a normal alpha-ANP concentration. Although none of the 13 children with atrial septal defect had heart failure, their mean (+/- SD) plasma alpha-ANP concentration (99.4 +/- 40.7 pg/mL) was significantly higher than that in control children (44.6 +/- 22.3 pg/mL). The plasma alpha-ANP concentration was significantly correlated with the pulmonary blood flow/systemic blood flow (Qp/Qs) ratio in the children with atrial septal defect. In the 34 children with ventricular septal defect the plasma alpha-ANP concentration increased in relation to increasing size of the defect. The plasma alpha-ANP concentration was significantly correlated with the Qp/Qs ratio, pulmonary artery pressure, and left atrial pressure, estimated from mean pulmonary artery wedge pressure, in the children with ventricular septal defect. In the children with tetralogy of Fallot, the mean plasma alpha-ANP concentration was normal, and mean right and left atrial pressures were not increased. The elevated alpha-ANP concentration in the three patients with heart failure decreased after their conditions improved with various treatments. Thus the measurement of alpha-ANP concentration may be valuable in evaluating the presence or absence of heart failure and the response to treatment in children with congenital heart diseases. Distention of the right and left atrial might induce the release of alpha-ANP in patients with atrial and ventricular septal defects, respectively.

Circulating atrial natriuretic polypeptide in essential hypertension

To investigate the significance of atrial natriuretic polypeptide (ANP) in essential hypertension, we measured plasma ANP concentration in 43 subjects with essential hypertension uncomplicated by cardiac or renal failure, in 16 subjects with borderline hypertension, and in 17 normotensive control subjects. Plasma ANP levels were significantly higher in hypertensive subjects compared to borderline hypertensive subjects ( p < 0.05) and normotensive control subjects ( p < 0.05). Hypertensive subjects with left ventricular hypertrophy (LVH) had higher plasma ANP levels than the hypertensive group as a whole ( p < 0.05). A significant positive correlation was observed between mean blood pressure and plasma ANP level in the hypertensive group (n = 43, γ = 0.77, p < 0.01). Furthermore, plasma ANP level was decreased significantly after 4 weeks of effective antihypertensive therapy compared with the initial value ( p < 0.05). These results suggest that plasma ANP is frequently elevated in hypertensive subjects with markedly high blood pressure or LVH, and it can be reduced by effective therapy with antihypertensive drugs.

Modulatory role of vasopressin in secretion of atrial natriuretic polypeptide in conscious rats.

To investigate whether vasopressin is involved in the secretory mechanism of atrial natriuretic polypeptide (ANP), effects of arginine-vasopressin (AVP) administered iv on plasma ANP levels were studied in conscious, unrestrained rats. The administration of 100 ng and 1 microgram of AVP caused a dose-dependent increase of the plasma ANP level, which was blocked by a V1-receptor antagonist of AVP, and was attenuated by 5 ml blood volume reduction before the stimulation. The injection of less than 10 ng of AVP induced no significant effects on ANP secretion. However, the administration of 5 ng of AVP significantly enhanced ANP secretion induced by intravascular volume expansion with 3 ml saline infusion. These results suggest the possible physiological significance of AVP as a modulator rather than a direct stimulator of ANP secretion from the heart.

Increase in Plasma Atrial Natriuretic Polypeptide (ANP) Following Sodium Load in Anesthetized Rats

Increase in Plasma Atrial Natriuretic Polypeptide (ANP) Following Sodium Load in Anesthetized Rats

Atrial natriuretic peptide correlates with pulmonary arterial pressure and cardiac output.

Correlations between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic parameters were studied in the central circulation of 12 patients with angina pectoris. The average plasma ANP level determined in the aorta was found to be 619 +/- 140 pg/ml. The plasma ANP levels showed a significant positive correlation with mean pulmonary arterial (PA) pressure, right ventricular pressure, and with cardiac index. In contrast, there was no significant correlation between plasma ANP levels and other hemodynamic variables including atrial pressure. These results suggest that hemodynamics other than the atrial pressure may have some role in modulating ANP secretion in certain pathological states.

Postural suppression of plasma atrial natriuretic polypeptide concentrations in man.

The effects of sequential changes in posture, from recumbency, to sitting and then to the upright position, each for 60 min, respectively, on the levels of plasma immunoreactive atrial natriuretic polypeptide (ANP) in healthy human subjects were studied using a radioimmunoassay (RIA) method. At the end of each change in posture, plasma ANP levels were respectively 150 +/- 16.4 pg/ml (recumbent), 103 +/- 11.2 pg/ml (sitting), and 78.1 +/- 7.90 pg/ml (upright). In contrast, plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) determined concomitantly with ANP showed a significant increase in response to the sitting and upright postures. Plasma ANP levels determined in normal subjects who remained in the recumbent posture for the same period did not show any significant change. This suggests that ANP is involved in the maintenance of haemodynamic homeostasis under physiological conditions and emphasizes that postural factors must be taken into account and controlled in order to evaluate plasma ANP levels properly, as well as those of PRC and PAC.

Effects of Captopril on Plasma Atrial Natriuretic Polypeptide and the Renin Angiotensin System in Rats

We investigated the effects of captopril on the plasma atrial natriuretic polypeptide (ANP) level and the renin angiotensin system in rats. A single oral administration of captopril decreased the plasma ANP level and increased the plasma renin activity (PRA). Chronic administration of captopril for 2 weeks caused no changes in plasma ANP level, but PRA was increased. This suggests the hypothesis that the hemodynamic changes rather than changes in the renin angiotensin system caused by captopril may affect the plasma ANP level.