Effects Of Atrial Natriuretic Polypeptide Research Articles

Effect of chronic central alpha-hANP administration on blood pressure, water and electrolyte balance in rats.

Relatively few studies have evaluated the chronic effects of atrial natriuretic polypeptide (ANP) administration into the central nervous system on peripheral cardiovascular and renal function under conditions of expanded extracellular fluid volume. The present investigation examined the effects of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) chronically infused into the cerebroventriculum of rats loaded with 0.9% saline. Measurements of the arterial blood pressure, water and electrolyte balances were carried out during a 4-day central ventricular infusion of alpha-hANP. Significant increases in daily urine volume and urinary sodium and chloride excretion were observed, but no changes of arterial blood pressure occurred. These results indicate that elevated levels of ANP in the CSF can influence sodium and water excretion, but do not appear to influence arterial pressure.

Clinical evaluation of plasma atrial natriuretic polypeptide in patients with respiratory failure in pulmonary tuberculosis

We previously reported the clinical role of plasma immunoreactive atrial natriuretic polypeptide (ANP) and cyclic GMP in patients with respiratory diseases, bronchial asthma (BA), chronic pulmonary emphysema (CPE) and pulmonary insufficiency induced by pulmonary tuberculosis (TBC). In this study, moreover, we divided patients with respiratory failure induced by tuberculosis sequelae into two groups, patients with oxygen therapy group [O2 (+) group] or ordinary practical treatment group [O2 (-) group], and we evaluated the difference of the roles of ANP in two groups and the correlation of ANP and c-GMP with clinical findings, blood gas analysis, electrocardiogram, chest roentogen photography and spirogram in two groups. In conclusion, the respiratory failure in patients with tuberculosis sequelae is compensated by increased cardiac output, and that causes the rising of right atrial pressure. These results show, addition to the basic effects of ANP, the concentration of plasma ANP is released with relating the degree of respiratory failure.

In vitro responses to atrial natriuretic polypeptide in human vessels commonly used as aortocoronary bypass grafts.

Vascular effects of atrial natriuretic polypeptide (APII), i.e. the peptide hormone released from the atrial myocardium, were investigated in segments of the human internal thoracic artery (ITA) and saphenous vein (SV) with intact (+E) or injured (-E) endothelium. All segments were subject to several cycles of agonists in order to detect tachyphylactic or facilitatory responses. Opposite, indirect effects on the noradrenaline contracted ITA and SV were obtained in response to APII at a supranormal concentration (50 nM) which had no direct relaxing action on the isolated segments in vitro. In ITA the noradrenaline contractures in subsequent cycles were reduced to 41 +/- 21% (+E) and 28 +/- 9% (-E), but in SV they were enhanced to 211 +/- 115% (+E) and 483 +/- 242% (-E) of those before APII exposure. Thus under in vitro conditions ITA could be indirectly relaxed by APII via tachyphylactic effect on the noradrenaline contracture. SV, on the other hand, was markedly potentiated by APII in its noradrenaline response. In injured endothelium these opposite effects were aggravated.

気管支ぜん息患者における血しょう心房性ナトリウム利尿ペプチドの臨床的役割

We previously reported that the atrial natriuretic polypeptide (ANP) caused a relaxant effect with the tissue cyclic GMP (c-GMP) levels on a guinea pig tracheal smooth muscle.We studied plasma immunoreactive ANP and c-GMP concentrations in various situations in patients with respiratory diseases which were divided into 3 groups, patients with bronchial asthma (BA, n=16), patients with chronic pulmonary emphysema (CPE, n=10) and patients with pulmonary insufficiency induced by pulmonary tuberculosis (Tbc, n=44). One hundred and thirteen healthy subjects were also studied as a control group. This is the first report that these clinical markers have been measured at same time in the field of respiratory diseases.In conclusion, 1) Plasma ANP was significantly higher in patients with BA (attack) (P<0.05) and Tbc (P<0.01) than in control. 2) Plasma c-GMP was significantly higher in patients with Tbc (P<0.01) than with BA (remission). 3) There was a significant correlation between plasma c-GMP and log ANP in patients with chronic respiratory disease (r=0.714, P<0.05, n=72). 4) Plasma ANP was significantly higher at attack than at remission (P<0.05).These results indicate that effects of ANP in patients with respiratory disease may be, at least in part, mediated by c-GMP being in the place of cyclic AMP, and ANP induced by pulmonary hypertention may cause a relaxant effect on tracheal and vascular smooth muscle. Therefore, exogenous ANP may also be useful on the therapy of patients with bronchial asthma. such as intractable asthma.

The significance of atrial natriuretic polypeptide in the cause of essential hypertension

The study was undertaken to clarify the role of atrial natriuretic polypeptide (ANP) in essential hypertension (EH). Plasma levels of alpha-human ANP (alpha hANP) were measured in 13 normal subjects, 25 patients with EH, 5 patients with primary aldosteronism (PA), 3 patients with renovascular hypertension (RVH) and 3 patients with pheochromocytoma (PC). Plasma level of alpha hANP (normal: 38.1 +/- 20.5pg/ml) was high in all hypertensive subjects. Synthetic alpha hANP was intravenously administrated to these subjects as follows: first a dose of 0.01 microgram/kg/min for 30 minutes, second a dose of 0.03 microgram/kg/min for 30 minutes, and then in normal subjects and EH 0.03 microgram/kg/min with a dose of 6.5 micrograms/kg/min of metoclopramide (MC) for 30 minutes. After the infusion of 0.01 microgram/kg/min alpha hANP, arterial blood pressure was significantly depressed in EH, RVH and PA, but not in PC. Marked diuretic and natriuretic responses were observed with increase in creatinine clearance and fractional sodium excretion in EH, RVH and PA, but not in PC. Sodium clearance/lithium clearance was slightly increased after infusion of 0.03 microgram/kg/min of alpha hANP in hypertensive subjects. Plasma renin activity did not change in low and normal renin EH and PA after infusion of either dose of alpha hANP, but was suppressed after 0.03 microgram/kg/min of alpha hANP in normal subjects and high renin EH, RVH and PC. Plasma aldosterone concentration was suppressed after either dose of alpha hANP in normal subjects and in EH, RVH and PC, but not in PA. Plasma cGMP concentration and urinary cGMP excretion were decreased after either dose of alpha hANP in both normal and hypertensive subjects. Furthermore, the decrease of PAC by alpha hANP was normalized by MC in normal subjects and EH. The rise in plasma cGMP by alpha hANP was suppressed by MC in both normal subjects and EH, but no changes were observed in arterial blood pressure and natriuretic response. These results suggest that alpha hANP secretion increases with elevation of blood pressure in EH, improving increase of circulatory blood volume, and alpha hANP may play a role in elevating blood pressure in EH. Moreover, it is considered that ANP increases sodium and water excretion through its effect on both renal glomeruli and distal tubules in EH. Hypotensive and natriuretic effects of ANP in EH may be concerned with dopaminergic activity which are probably related to the production of cGMP in the vascular wall and inhibition of the excretion of aldosterone in the adrenal cortex.

The Significance of cGMP and Dopamine Receptor on the Natriuretic and Hypotensive Activities of Synthetic Atrial Natriuretic Polypeptide in Essential Hypertension

This study was undertaken to clarify the role of dopamine receptor (DA2) on the effects of atrial natriuretic polypeptide(ANP) on blood pressure, plasma and urinary cyclic GMP, and urinary sodium excretion, alpha-human ANP (alpha-hANP) was intravenously administrated to 7 normal subjects and 14 patients with essential hypertension as follows: first a dose of 0.01 micrograms/kg/min for 30 minutes, and then 0.03 micrograms/kg/min with or without metoclopramide(MC) for 30 minutes. After the infusion of the 0.03 micrograms/kg/min dose of alpha-hANP, systolic blood pressure fell from 115 +/- 17 mmHg to 109 +/- 15 mmHg in normal subjects, and fell significantly from 163 +/- 33 mmHg to 145 +/- 26 mmHg in patients with essential hypertension. Diastolic blood pressure fell from 101 +/- 14 mmHg to 92 +/- 7 mmHg in patients with essential hypertension but did not change in normal subjects. A dose of 0.03 micrograms/kg/min of alpha-hANP led to a threefold rise in urine volume and twofold rise in urinary sodium excretion in normal subjects, and a fivefold rise in urine volume and fourfold rise in urinary sodium excretion in patients with essential hypertension. However, there was no relationship between the hypotensive and natriuretic effects of alpha-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03 micrograms/kg/min dose of alpha-hANP increased plasma cyclic GMP concentration from 4.1 +/- 2.1 pmol/ml to 34.3 +/- 25.Opmol/ml in normal subjects and from 4.5 +/- 2.6 pmol/ml to 20.3 +/- 7.4 pmol/ml in patients with essential hypertension. The rise in plasma cyclic GMP by alpha-hANP was suppressed by MC both in normal subjects and patients with essential hypertension. Urinary cyclic GMP excretion also increased during the infusion of alpha-hANP, but this effect was not suppressed by MC. Furthermore, plasma aldosterone concentration (PAC), which was depressed by alpha-hANP in normal subjects and patients with essential hypertension, was increased by MC. These results suggest that the hypotensive effect of alpha-hANP may depend not only on the natriuretic effect, but also on vasodilatation, the inhibition of aldosterone production or the suppression of the sympathoadrenomedullary system. Cyclic GMP may be produced through the DA2 receptor in vascular tissue but not in the kidney.

Decreased renal responses to atrial natriuretic peptide in renal wrap hypertension.

1. The effects of atrial natriuretic polypeptide (ANP) on renal function were examined in renal wrap hypertensive rabbits and sham operated rabbits. 2. ANP (2 micrograms/min) induced hypotension, but did not produce significant diuresis, natriuresis or change in the glomerular filtration rate (GFR) in renal wrap hypertensive rabbits (n = 8). 3. In sham operated normotensive rabbits (n = 4), ANP induced significant diuresis (230%) and increased GFR by about 40%. 4. Thus, ANP was markedly less effective in the impaired kidneys of renal wrapped rabbits than in normal kidneys.

Effects of atrial natriuretic polypeptide and organic nitrates on levels of relaxation and cyclic nucleotide of canine coronary artery with and without endothelial injury.

We studied the effects of organic nitrates and human atrial natriuretic polypeptide (hANP) on relaxation and tissue cyclic guanosine monophosphate (cGMP) levels using isolated canine coronary arteries with and without endothelial injury. Glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), pentaerythritol tetranitrate (PETN), and hANP relaxed both the injured and control coronary arteries, and they increased tissue cGMP levels in a dose-dependent fashion without changing tissue adenosine 3':5'-cyclic phosphate (cAMP) levels. The extent of relaxation was larger and the increase in cGMP was greater in the injured coronary artery than in the control artery. Methylene blue inhibited relaxation induced by GTN and hANP, and decreased tissue cGMP levels in both the injured and control groups. M&B 22,948 enhanced relaxation induced by GTN and hANP and increased tissue cGMP levels in both groups. The results suggest that organic nitrates and hANP relax the coronary artery by directly activating the guanylate cyclase in coronary smooth muscle and that such activation is independent of the endothelium-dependent vasodilator system.

Effects of human atrial natriuretic polypeptide on pancreatic exocrine secretion in the dog

We examined the effects of atrial natriuretic polypeptide (hANP) on exocrine function in the isolated and blood-perfused dog pancreas in situ. Intra-arterial injection of hANP (1–10 μg) resulted in the dose-dependent increases of the pancreatic juice secretion. The secretory activity of 3 μg of hANP was approximately equal to one third of the secretory activity of 0.1 units of secretin. The use of hANP increased the concentration of bicar-bonate but not that of sodium and protein in the pancreatic juice as compared with the basal values. These secretory responses to hANP were not inhibited by treatment with haloperidol, sulpiride, phentolamine, propranolol, atropine, cimetidine or ethacrynic acid. These results suggest that hANP acts directly on the pancreatic exocrine gland to stimulate pancreatic secretion; without, however, increasing sodium excretion. The mechanism of this effect remains to be elucidated.

Effects of dopamine and synthetic atrial natriuretic polypeptide on the release of norepinephrine and epinephrine from the adrenal medulla of rats

We evaluated the effects of dopamine (DA) and synthetic atrial natriuretic polypeptide (ANP) on the release of catecholamines (CA) from the adrenal medulla. Adrenal glands of male Wistar rats were superfused with Ringer's solution saturated with 95%, O2, 5% CO2 by the use of a continuous flow incubation system, and norepinephrine (NE) and epinephrine (E) concentrations in the perfusate were continuously measured by high pressure liquid chromatography with fluorescent reaction. And the effects of DA and ANP on the CA release were evaluated. Next the effects of metoclopramide (MC), dopamine (D2) antagonist, and glucagon were added in the Ringer's solution, and the changes of NE and E in the perfusate were determined. Basal secretion of NE and E were 0.02-0.04 ng/mg.wet weight/min and 0.05-0.1 ng/mg.wet weight/min, respectively. DA remarkably decreased both NE and E release, and the suppressive effect was dependent on DA concentration in the perfusate. MC clearly raised NE and E release as well as glucagon. The increasing effect of MC was perfectly suppressed by 10(-4) M of DA. But the effect of glucagon was not blocked by the same dose of DA. Alpha rANP (10(-5)M) slightly decreased the releases of NE and E from adrenal medulla, and the magnitude of the effect of rANP was smaller than that of DA. MC significantly increased NE and E release even when the adrenal gland was superfused with Ringer's solution containing 10(-5)M of rANP. These data suggest that the release of CA from adrenal medulla may be regulated by DA, and that the receptors specifically binding to DA may exist in adrenal medulla as well as sympathetic presynaps. We concluded that DA (but not ANP) may play an important role in controlling (suppressing) the activity of sympathoadrenomedullary system.

Stimulated Corticosterone Production by α-Human Atrial Natriuretic Polypeptide with Increased Cyclic GMP Production

Several studies on the effects of atrial natriuretic polypeptide (ANP) on aldosterone production using isolated adrenal cells have been reported, and they have consistently demonstrated the reduced production of aldosterone by ANP. However, the results on the corticosterone production are sundry. Since ANP selectively activates particulate guanylate cyclase, a possibility could exist that cyclic GMP is the second messenger of ANP signal transduction. In order to demonstrate unequivocally a correlation of cyclic nucleotide levels with the ANP-induced steroidogenesis, we investigated the effects of various concentrations of alpha-human atrial natriuretic polypeptide (alpha-hANP) on aldosterone, corticosterone, cyclic AMP and cyclic GMP production in isolated glomerulosa and fasciculata cells of the rats. Rat glomerulosa and fasciculata cells were obtained by enzymatic digestion of the adrenals of male Wistar rats. The cell pellet was suspended in Hanks balanced salt solution-0.1% BSA buffer and distributed in 900 microliter aliquots to 12 X 75 mm glass tubes. The samples were preincubated for 90 min. in a 37 degrees C water bath under an atmosphere of 5% CO2/95% O2. Aliquots of the test samples were added in a 100 microliter volume and incubated for 4 hr. Total volume of the incubation mixture is 1.0 ml. Aldosterone, cyclic AMP and cyclic GMP were measured by radioimmunoassay and corticosterone was determined by fluorimetric method. The results indicated that alpha-hANP inhibited the secretion of aldosterone and corticosterone in rat glomerulosa cells. Alpha-hANP significantly decreased cyclic AMP production in the rat glomerulosa cells, while it markedly stimulated cyclic GMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of human alpha-atrial natriuretic polypeptide on adrenocortical function in man.

To determine the effects of atrial natriuretic polypeptide (ANP) on plasma levels of ACTH, cortisol, aldosterone and dehydroepiandrosterone (DHEA), synthetic human alpha-ANP (h alpha-ANP) was infused i.v. into eight normotensive, disease-free volunteers, at a dose and duration previously found to be sufficient to produce apparent cardiovascular and renal effects. The mean basal concentration of plasma ACTH determined by radioimmunoassay was 18.2 +/- 3.1 ng/l. Plasma ACTH concentrations tended to be decreased during the infusion in all subjects. However, the change in plasma ACTH concentrations during infusion of h alpha-ANP was essentially the same as that during the infusion of saline. The mean plasma cortisol concentration was significantly suppressed from 25 to 40 min after the end of synthetic h alpha-ANP infusion. At 90 min after infusion, the mean plasma level of cortisol reverted to the pretreatment level. There was a non-significant increase in plasma renin activity following the infusion. The mean plasma aldosterone concentration was reduced by 15% (P less than 0.05) during the infusion and returned to preinfusion levels 10 min after termination of the infusion, after which the mean plasma concentration declined to the level seen during infusion. Administration of h alpha-ANP had no significant influence on plasma DHEA concentrations, but there was a tendency to decrease during the infusion. Our data suggest that synthetic h alpha-ANP inhibits adrenocortical steroidogenesis in man.

Additive effects of atrial natriuretic polypeptide and of renal vasodilating agents in the anesthetized dog

In order to examine the contribution of an increase in renal papillary plasma flow to the mechanism of natriuresis by atrial natriuretic polypeptide (ANP), we compared the natriuretic effects of ANP administered into the renal artery of the dog together with secretin or acetylcholine (ACh). At an equivalent renal vasodilating dose, ACh increased urinary excretion of sodium (U NaV) to 212 ± 36% of the control associated with a decrease in urine osmolality (62 ± 6%), whereas secretin did not change U NaV (113 ± 12%) or urine osmolality (101 ± 14%). This result was compatible with the view that ACh causes natriuresis mainly by increasing papillary plasma flow. Combined administration of ANP with secretin caused a marked increase in U NaV to 407 ± 55%, in association with a decrease in urine osmolality to 55 ± 9%, suggesting that ANP may cause natriuresis by a mechanism similar to that of ACh. Combined administration of ANP with ACh further increased U NaV to 323 ± 67% and decreased urine osmolality to 50 ± 6%. These observations suggest that ANP and ACh share common but not identical mechanisms of natriuretic action since ANP caused additional natriuresis during ACh infusion. These findings, however, do not necessarily exclude the possibility that ANP also inhibits renal sodium reabsorption by a direct action.