Atrial natriuretic peptide inhibits osmolality-induced arginine vasopressin release in man

1. Eight normal volunteers were infused with 5% saline (5 g of NaCl/100 ml) at a rate of 0.06 ml min-1 kg-1 for 120 min to increase plasma osmolality and plasma arginine vasopressin. Human atrial natriuretic peptide (alpha-hANP; 100 micrograms) or placebo was given in random order in a double-blind cross-over design for the last 20 min of the saline infusion. 2. Compared with the placebo infusion, atrial natriuretic peptide (ANP) produced a 43% greater sodium excretion and a 34% greater urinary volume in the subsequent hour. 3. Mean plasma immunoreactive ANP did not increase in response to changes in osmolality and rose to a peak of 118 pg/ml during the alpha-hANP infusion. alpha-hANP produced significant suppression of mean plasma arginine vasopressin over the 60 min after the infusions. 4. We conclude that ANP is not released in response to increased osmolality in vivo, and that it inhibits osmolality-induced arginine vasopressin release in man.     

Renal, haemodynamic and hormonal interactions between atrial natriuretic factor and arginine vasopressin in patients with congestive heart failure.

1. Nine patients with compensated heart failure were infused with synthetic arginine vasopressin at a rate of 0.1 m-units min-1 kg-1 for 60 min to increase their plasma arginine vasopressin concentration. Synthetic human atrial natriuretic factor (3 pmol min-1 kg-1) or placebo was co-infused with the arginine vasopressin in random order in a single-blind cross-over design. 2. The resultant plasma concentrations of arginine vasopressin and atrial natriuretic factor fell to within the upper range observed in congestive heart failure. Compared with the infusion of arginine vasopressin alone, atrial natriuretic factor co-infusion enhanced both the urine flow rate and the sodium excretion rate (both P less than 0.05) without significant haemodynamic and hormonal effects. 3. Systematic blood pressure was elevated by arginine vasopressin infusion (P less than 0.05) without any change in heart rate. Co-infusion of atrial natriuretic factor did not affect these haemodynamic parameters. 4. These results suggest that an increased release of atrial natriuretic factor maintains water and sodium excretion in the presence of arginine vasopressin-induced renal modulations, and that the pressor effect of arginine vasopressin is not antagonized by the increased plasma level of atrial natriuretic factor in patients with congestive heart failure.     

The osmotic thresholds for thirst and vasopressin release are similar in healthy man

The relationship between thirst perception and plasma osmolality was studied during hypertonic and physiological saline infusion in ten healthy volunteers. Thirst perception was quantified using a linear visual analogue scale which volunteers marked at intervals during the infusion periods. Infusion of hypertonic saline caused a steady rise in plasma osmolality together with a progressive linear increase in thirst perception and also plasma arginine vasopressin. No significant changes in thirst, plasma osmolality or plasma arginine vasopressin occurred during infusion of physiological saline. Linear regression analysis of the results defined the functions. Thirst (cm) = 0.3 (plasma osmolality-281) (r = +0.92, P less than 0.001) and plasma arginine vasopressin (pmol/l) = 0.4 (plasma osmolality-285) (r = +0.96, P less than 0.001). The osmolar threshold for thirst onset thus defined (281 mosmol/kg) was much lower than in previous studies and similar to the theoretical osmolar threshold for vasopressin release (285 mosmol/kg). We conclude that thirst perception rises in a progressive fashion throughout a wide range of plasma osmolality and that the osmolar threshold for thirst onset is similar to the theoretical osmolar threshold for vasopressin release. The results are compatible with the concept of either a single osmoreceptor subserving both thirst and vasopressin release, or two osmoreceptors sharing similar functional characteristics.     

Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus

1. Osmotically stimulated thirst and vasopressin release were studied during infusions of hypertonic sodium chloride and hypertonic D-glucose in euglycaemic clamped diabetic patients and healthy controls. 2. Infusion of hypertonic sodium chloride caused similar elevations of plasma osmolality in diabetic patients (288.0 +/- 1.0 to 304.1 +/- 1.6 mosmol/kg, mean +/- SEM, P less than 0.001) and controls (288.6 +/- 0.9 to 305.7 +/- 0.6 mosmol/kg, P less than 0.001), accompanied by progressive increases in plasma vasopressin (diabetic patients, 0.9 +/- 0.3 to 7.7 +/- 1.5 pmol/l, P less than 0.001; controls 0.5 +/- 0.1 to 6.5 +/- 1.0 pmol/l, P less than 0.001) and thirst ratings (diabetic patients 1.0 +/- 0.2 to 7.1 +/- 0.5 cm, P less than 0.001; controls 1.8 +/- 0.4 to 8.0 +/- 0.5 cm, P less than 0.001) in both groups. 3. Drinking rapidly abolished thirst and vasopressin secretion before major changes in plasma osmolality occurred in both diabetic patients and healthy controls. 4. There were close and significant correlations between plasma vasopressin and plasma osmolality (diabetic patients, r = +0.89, controls r = +0.93) and between thirst and plasma osmolality (diabetic patients r = +0.95, controls r = +0.97) in both diabetic patients and healthy controls during hypertonic saline infusion. 5. Hypertonic D-glucose infusion caused similar elevations in blood glucose in diabetic patients (4.0 +/- 0.2 to 20.1 +/- 1.2 mmol/l, P less than 0.001) and healthy controls (4.3 +/- 0.1 to 19.3 +/- 1.2 mmol/l, P less than 0.001) but did not change plasma vasopressin or thirst ratings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of lithium on the renal actions of alpha-human atrial natriuretic peptide in normal man

1. alpha-Human atrial natriuretic peptide (7.5 pmol min-1 kg-1) was infused intravenously into eight healthy men after pretreatment with lithium carbonate (750 mg) or placebo. 2. Baseline sodium excretion was significantly increased after lithium, but the natriuresis during infusion of alpha-human atrial natriuretic peptide was attenuated. 3. Similar decreases in plasma renin activity with infusion of alpha-human atrial natriuretic peptide occurred on both days. 4. Administration of lithium may be associated with pharmacological effects and further work is required to validate the use of lithium clearance as a marker of proximal renal tubular sodium handling.     

Atrial natriuretic peptide: evidence of action as a natriuretic hormone at physiological plasma concentrations in man

The administration of exogenous atrial natriuretic peptide (ANP) causes a natriuresis and diuresis in man, but this has, to date, only been demonstrated at plasma ANP concentrations within the high pathological or pharmacological ranges. Evidence that ANP acts physiologically requires the demonstration of a natriuretic effect when it is infused to recreate plasma concentrations similar to those observed after physiological stimuli. We infused human alpha-ANP (1-28) at a calculated rate of 1.2 pmol min-1 kg-1 for 3 h into seven water-loaded normal subjects, achieving plasma ANP concentrations within the upper part of the physiological range. The subjects' resting plasma ANP concentration increased from 3.8 +/- 1.5 to 20.9 +/- 1.9 pmol/l. The infusion of ANP caused a 60% increase of mean urinary sodium excretion from 111 +/- 18 to 182 +/- 30 mumol/min (P less than 0.001) and a 28% increase of mean water excretion from 10.8 +/- 0.8 to 13.8 +/- 1.6 ml/min (P less than 0.01). The infusion suppressed mean plasma renin activity from 1.55 +/- 0.10 to 1.17 +/- 0.06 pmol of ANG I h-1 ml-1 (P less than 0.001). Mean plasma aldosterone concentration (242 +/- 16 basally and 215 +/- 15 pmol/l at the end of ANP infusion) did not change significantly. Pulse rate and blood pressure were unchanged throughout the study. No significant change in any of the variables mentioned above occurred during the infusion of the vehicle alone on a separate study day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of atrial natriuretic factor on bronchomotor tone in the normal human airway

1. Asthmatic patients bronchodilate in response to infused atrial natriuretic factor. We wished to determine whether the airways of normal subjects responded in a similar way. 2. Changes in airway resistance, as determined by specific airway conductance, were measured in eight normal subjects in response to intravenous infusion of atrial natriuretic factor at doses of 0.5, 2 and 10 pmol min-1 kg-1. 3. No significant effect was observed on specific airway conductance at any rate of infusion despite maximum mean (SEM) plasma levels of 597 (62) pg of atrial natriuretic factor/ml in peripheral venous blood. 4. A second study was performed using six of the eight original subjects and employing a pharmacological dose of 50 pmol of atrial natriuretic factor min-1 kg-1. This produced mean plasma levels of 2056 pg/ml and a mean increase of 31% in specific airway conductance. 5. It is concluded that pharmacological, but not pathophysiological, elevations of plasma atrial natriuretic factor may significantly alter bronchomotor tone in normal subjects.     

Low dose infusion of atrial natriuretic peptide causes salt and water excretion in normal man

1. The effects of low dose infusion of atrial natriuretic peptide (ANP) were observed in double-blind, placebo-controlled study in six fluid-loaded volunteers. After baseline observations, hourly increments of 0.4, 2 and 10 pmol min-1 kg-1 were infused with continuous observation of heart rate, blood pressure and cardiac output. Plasma ANP, aldosterone, and catecholamines, and urinary volume and sodium excretion, were estimated at half-hourly intervals. 2. ANP infusion resulted in an increase of 35, 98 and 207% in urinary sodium excretion and of 10, 20 and 71% in urinary volume when compared with placebo. Plasma ANP was markedly elevated above placebo levels only during infusion of 10 pmol of ANP min-1 kg-1. 3. No change in heart rate of blood pressure was noted during the study, but a significant fall in stroke volume index was observed during active treatment. Plasma levels of aldosterone and catecholamines were not significantly different on the 2 treatment days. 4. The potent natriuretic and diuretic effects of this peptide at plasma concentrations not significantly elevated from physiological suggest a hormonal role for ANP in the homoeostasis of salt and water balance.     

Carbidopa does not affect the renal response to atrial natriuretic factor in man

1. The dependence of atrial natriuretic factor on renal dopamine for its renal effects in man was examined in 10 healthy volunteers using the dopa decarboxylase inhibitor carbidopa. 2. Each volunteer attended on two occasions, and received an infusion of atrial natriuretic factor (4 pmol min-1 kg-1) for 60 min after pretreatment with either placebo or carbidopa orally. These were administered in random, double-blind fashion. 3. A similar increase in plasma atrial natriuretic factor concentration was seen after atrial natriuretic factor infusion on both visits. 4. Infusion of atrial natriuretic factor produced a small unsustained rise in urinary dopamine excretion. This increase in urinary dopamine excretion was blocked by carbidopa with no effect on the natriuresis. 5. Urinary guanosine 3':5'-cyclic monophosphate excretion increased in response to the atrial natriuretic factor infusion whether placebo or carbidopa was given. Guanosine 3':5'-cyclic monophosphate, but not dopamine, may be a mediator of the renal response to atrial natriuretic factor in man.     

Atrial natriuretic peptide: an endogenous factor enhancing sodium excretion in man

For many years experimental evidence has suggested the existence of a circulating factor able to enhance sodium excretion. Very recently peptides with natriuretic activity in experimental animals have been isolated from mammalian and human cardiac tissue. In order to determine whether this natriuretic activity has relevance to man we have studied the effects of an infusion of alpha-human atrial natriuretic peptide (alpha-h-ANP) in normal subjects. Sodium excretion trebled (P = less than 0.005) during the infusion of a calculated dose of 15 pmol of alpha-h-ANP min-1 kg-1 and there was an accompanying diuresis; radioimmunoassay of plasma alpha-h-ANP during the natriuresis indicated a mean peak incremental concentration of 203 +/- 78 (SEM) pmol/l. The infusion of a calculated dose of 1.5 pmol min-1 kg-1 did not affect sodium excretion. There were no haemodynamic changes and no side effects were noted.     

Role of atrial natriuretic factor in changes in the responsiveness of aldosterone to angiotensin II secondary to sodium loading and depletion in man

1. Sodium loading blunts the response of aldosterone to infusion of angiotensin II, whereas sodium depletion leads to an enhanced response. The hypothesis was tested that these changes in responsiveness of the zona glomerulosa are mediated in part by changes in plasma atrial natriuretic factor levels. 2. To this end, plasma renin activity and plasma aldosterone were measured in the upright and recumbent position and during incremental infusions of angiotensin II (1, 3 and 6 ng of angiotensin II amide min-1 kg-1 for 1 h each dose) after 6 days of sodium loading (study 1), after 5 days of sodium depletion (study 2) and after sodium depletion plus infusion of atrial natriuretic factor (0.13 microgram/min for 8 h) on the test day (study 3). Six normal young males were investigated. 3. Plasma atrial natriuretic factor levels were around 5 pmol/l in study 2, 15 pmol/l in study 1 and 15 pmol/l in study 3 during infusion of atrial natriuretic factor. Two hours after the onset of atrial natriuretic factor infusion, plasma renin activity and plasma aldosterone (recumbent) were markedly and significantly lower in study 3 than in study 2, but still significantly higher than in study 1. The increase in plasma aldosterone after infusion of angiotensin II was slightly, but not significantly, blunted by infusion of atrial natriuretic factor in study 3 compared with study 2. The overall increase in plasma aldosterone was still significantly greater in study 3 than in study 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal haemodynamic, hormonal and excretory effects of low-dose atrial natriuretic factor infusion in renal transplant recipients.

1. In experimental studies, activation of renal sympathetic nerves attenuates the natriuretic response to atrial natriuretic factor. We therefore investigated the response to low-dose infusion of atrial natriuretic factor in renal transplant recipients. 2. Eight male cyclosporin-treated renal transplant recipients received human-alpha atrial natriuretic factor (1-28) at a dose of 1.2 pmol min-1 kg-1 or placebo for 2 h in a placebo-controlled, randomized, cross-over study. The plasma atrial natriuretic factor concentration rose from 18.5 to 49.2 pmol/l in association with an immediate natriuresis (a rise of 49.1 mumol/min in the first 30 min, P less than 0.05; peaking at a 61% increase from baseline, P less than 0.01), diuresis (from 3.37 to 7.46 ml/min) and a threefold rise in urinary cyclic GMP excretion. 3. In response to infusion of atrial natriuretic factor, the packed cell volume rose by 4.2% (P less than 0.001) and the filtration fraction by 5% (from 22 to 27%, P less than 0.05), but there was no significant change in renal plasma flow, glomerular filtration rate or mean arterial blood pressure. Likewise, the plasma catecholamine concentrations, plasma renin activity and serum erythropoietin concentration remained unchanged. 4. The sensitivity of the renal allograft to plasma atrial natriuretic factor concentrations in the high physiological range suggests a role for endogenous atrial natriuretic factor in the modulation of graft function. Furthermore, the immediate natriuretic response to atrial natriuretic factor in the effectively denervated transplant kidney, in contrast to the delayed response seen in normal subjects, may imply that sympathetic nerves have an inhibitory effect on the renal response to atrial natriuretic factor in normal man.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide blocks the renal vasoconstrictor response to hypertonic saline in the dog

The role of atrial natriuretic peptide to modulate the renal tubuloglomerular feedback response was examined in the dehydrated anesthetized dog using an infusion of hypertonic sodium chloride to increase renal plasma sodium concentration by 30 mEq/l as the stimulus to activate the tubuloglomerular feedback. Two sequential infusions of hypertonic sodium chloride into the renal artery for 10 min were separated by 90 min, and various interventions were introduced before the second hypertonic saline infusion. In the first group of dogs, the first infusion of hypertonic saline resulted in a significant decrease in renal blood flow from 234 +/- 36 to 199 +/- 31 ml/min, but when atriopeptin III (APIII) was infused into the renal artery at 3 x 10(-10) mol/min, the repeat infusion of hypertonic saline resulted in a significant increase in blood flow from 221 +/- 28 to 269 +/- 35 ml/min that was maintained throughout the 10 min of hypertonic saline. In the second group of dogs only the vehicle for APIII was infused during the second hypertonic saline infusion. In these dogs, renal blood flow decreased significantly the first time from 201 +/- 17 to 170 +/- 16 ml/min, and the second time from 232 +/- 22 to 177 +/- 20 ml/min. In a third group of dogs, the vasodilator sodium nitroprusside, a stimulator of smooth muscle soluble guanylate cyclase, was infused into the renal artery during the second hypertonic saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pressor effect of arginine vasopressin in progressive autonomic failure

The blood pressure (BP) and heart rate (HR) responses to 5 min incremental intravenous infusions of noradrenaline (NA) and arginine vasopressin (AVP) were investigated both in patients with progressive autonomic failure (PAF) and in normal volunteers. Stepwise infusion of NA at rates of 300-3000 pmol min-1 kg-1 produced a bradycardia and a dose related increase in BP in normal subjects. In subjects with PAF there was no significant HR response but the dose-BP response was shifted to the left with significant pressor responses at infusion rates of 60-300 pmol min-1 kg-1. Stepwise infusion of AVP at 0.2-5.0 pmol min-1 kg-1 caused transient bradycardia but no pressor response in seven normal volunteers. Further increases in AVP infusion in three other subjects achieved plasma AVP levels as high as 3000-4000 pmol/l, and still no significant pressor response was observed. Stepwise infusion of AVP at 0.05-2.0 pmol min-1 kg-1 in the eight subjects with PAF resulted in a pressor response without any change in HR. During this infusion plasma AVP increased from 0.8 +/- 0.2 (mean +/- SEM) to 30 +/- 2 pmol/l. A significant pressor response was already apparent at a plasma AVP level of 5.5 +/- 1.8 pmol/l.     

Prolonged decrease in blood pressure after atrial natriuretic peptide infusion in essential hypertension: a new anti-pressor mechanism?

1. To study the anti-hypertensive effects of atrial natriuretic peptide (ANP), eight patients with mild to moderate essential hypertension, on no treatment, were infused with alpha-human ANP (102-126) (37 pmol min-1 kg-1) or placebo for 60 min and observed for a further 4 h on the fifth day of low and high sodium diets in a randomized, cross-over study. 2. Plasma ANP levels increased over 30-fold into the high pathophysiological range during ANP infusion, but had returned to control values by 60 min after the end of infusion. With ANP infusion, there was a large decrease in supine blood pressure which was similar on both the low and high sodium intakes and was maximal 20-40 min after completion of the infusion. These reductions in blood pressure were sustained for a further 4 h after the end of ANP infusion and for 3 h after plasma ANP levels had returned to control values. 3. Maximal urinary sodium excretion increased 10-fold on the low sodium diet (negative sodium balance 20 mmol) and threefold on the high sodium diet (negative sodium balance 30 mmol) during ANP infusion; however, during the 4 h after infusion, urinary sodium excretion was below placebo values. During ANP infusion, packed cell volume increased significantly on both diets but returned to control values by 4 h after the end of infusion. 4. There were no significant changes in plasma renin activity compared with placebo during or after ANP infusion. However, plasma aldosterone was significantly greater than placebo values after the end of ANP infusion on both low and high sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clearance of brain natriuretic peptide in patients with chronic heart failure: indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism.

1. Brain natriuretic peptide is a new natriuretic hormone with striking similarity to atrial natriuretic peptide, but there are no previous data concerning its clearance in man. Two pathways of clearance for atrial natriuretic peptide are recognized: degradation by neutral endopeptidase and binding to atrial natriuretic peptide clearance receptors. We have examined the effect of candoxatril, an inhibitor of neutral endopeptidase (dose range 10-200 mg), and the effect of an infusion of a pharmacological dose [45 micrograms (90 micrograms in two patients)] of synthetic human atrial natriuretic peptide on plasma human brain natriuretic peptide-like immunoreactivity levels in seven patients with mild to moderate chronic heart failure. 2. Plasma human brain natriuretic peptide-like immunoreactivity levels were elevated in all patients (mean +/- SEM 22.0 +/- 6.2 pmol/l) compared with healthy control subjects (1.3 +/- 0.2 pmol/l, n = 11). 3. In all patients, candoxatril increased both plasma atrial natriuretic peptide (P less than 0.05) and plasma human brain natriuretic peptide-like immunoreactivity (P less than 0.05) levels. 4. By contrast, an exogenous infusion of atrial natriuretic peptide had no effect on plasma human brain natriuretic peptide-like immunoreactivity levels despite increasing the plasma atrial natriuretic peptide concentration to 424 +/- 74 pmol/l, which is a level of atrial natriuretic peptide which would have 'swamped' all atrial natriuretic peptide clearance receptors. 5. We have therefore shown that plasma human brain natriuretic peptide-like immunoreactivity levels in chronic heart failure are increased by a neutral endopeptidase inhibitor, but are unchanged by an exogenous infusion of atrial natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)     

The reproducibility and heritability of individual differences in osmoregulatory function in normal human subjects

The rise in plasma vasopressin produced by infusion of hypertonic saline varies widely among healthy adults. To determine if these interindividual differences are reproducible, we used linear regression to analyze the relationship of plasma vasopressin to plasma osmolality during repeat hypertonic saline infusion in seven normal subjects. The results confirmed that the slope or sensitivity of the relationship differed widely between subjects (0.12 to 1.66 pg/ml/mOsm/kg) and revealed that these differences were highly reproducible. (r = 0.94 on repeat testing). The individual values for osmotic threshold were less variable (280 to 288 mOsm/kg) as well as less clearly reproducible (r = 0.61). To determine whether these differences are genetically influenced, we compared the vasopressin osmolality relationships within seven monozygotic and six dizygotic twin pairs. We found that the threshold and sensitivity values correlated significantly within monozygotes (r = 0.95 and 0.95) but not within dizygotes (r = 0.34 and 0.21). When the osmoregulation of thirst was similarly evaluated, the individual relationships were as variable as for plasma vasopressin, but only the threshold values in monozygotes correlated significantly (r = 0.92). In 80 healthy adults, the frequency distributions of the osmotic threshold and sensitivity of the vasopressin responses were essentially normal. We conclude that the sensitivity for vasopressin secretion as well as the osmotic thresholds for thirst and vasopressin demonstrate significant polygenetic variance among healthy adults.     

Differential effects of atrial natriuretic peptide and dopamine on urinary protein excretion in chronic glomerulonephritis.

1. To examine whether or not atrial natriuretic peptide-induced proteinuria simply results from increases in urine flow or glomerular filtration rate, we infused dopamine (1 microgram min-1 kg-1) and alpha-human atrial natriuretic peptide (0.025 microgram min-1 kg-1) into nine patients with chronic glomerulonephritis and nine essential hypertensive patients without renal damage, and compared the effects of the two agents on renal function and urinary protein excretion. 2. In patients with chronic glomerulonephritis, dopamine infusion significantly increased urinary sodium excretion (+59%), renal blood flow (+20%) and creatinine clearance (+14%). However, urinary protein excretion was not changed. Addition of atrial natriuretic peptide to the dopamine infusion further increased urinary sodium excretion and maintained creatinine clearance at the same level. In contrast to the infusion of dopamine alone, atrial natriuretic peptide markedly increased urinary protein excretion (77 versus 229 mg min-1 m2, P less than 0.02). Furthermore, the addition of atrial natriuretic peptide elevated the urinary protein/creatinine ratio (1.55 versus 5.35, P less than 0.05), while dopamine alone did not (1.55 versus 1.45, not significant). 3. In essential hypertensive patients, dopamine and dopamine plus ANP showed renal effects similar to those of chronic glomerulonephritis; however, the urinary excretion of protein was not changed significantly. 4. These results suggest that atrial natriuretic peptide may increase urinary protein excretion mainly by increasing the permeability of the damaged glomeruli to protein rather than by simply increasing urine flow or glomerular filtration. Possible mechanisms underlying the proteinuria-increasing effects of atrial natriuretic peptide are discussed.     

Effects of pancreatic polypeptide on motilin and circulating metabolites in man

Pancreatic polypeptide was infused intravenously in healthy fasting subjects at 1 pmol kg-1 (n = 7) and 4 pmol kg-1 min-1 (n = 10) producing plasma PP concentrations of 223 +/- 37 pmol/l (mean +/- SEM) and 891 +/- 64 pmol/l respectively. These levels are similar to and four-fold higher than those seen after a normal mixed breakfast in healthy young adults. In a separate study five healthy subjects ingested a small breakfast during infusion of PP on different days at 1 pmol kg-1 min-1 and 2 pmol kg-1 min-1 respectively. PP at 1 pmol kg-1 min-1 caused a marked reduction in fasting plasma motilin concentrations to 20% of the basal level (p less than 0.001). There were, however, no significant changes in plasma concentrations of insulin, glucagon, gastrin, secretin, enteroglucagon, gastric inhibitory peptide or neurotensin. Despite previous reports possibly implicating PP in metabolism, there were no significant effects on blood levels of glucose, alanine lactate, 3-hydroxybutyrate, glycerol or non-esterified fatty acids, either in the fasting state or after the ingestion of food. Although it seems unlikely that PP is a major hormonal regulator of intermediary metabolism in man, its ability to suppress motilin at physiological concentrations suggests the possibility of an indirect influence on digestive motor function.     

Effect of alpha-human atrial natriuretic peptide on proteinuria in patients with primary glomerular diseases

1. The effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) on urinary protein excretion were examined in nine healthy subjects and 20 patients with primary glomerular diseases who had proteinuria of 1.0 g or more per day. Synthetic alpha-hANP was intravenously infused into supine subjects at a rate of 8.3 pmol min-1 kg-1 for 40 min. 2. Before alpha-hANP infusion, the plasma concentration of immunoreactive alpha-hANP was significantly higher in the patients with glomerulonephritis than in the normal subjects (44.3 +/- 8.7 vs 19.4 +/- 3.0 pmol/l, mean +/- SEM, P less than 0.01) and it showed a positive correlation with mean arterial pressure (rs = 0.84, P less than 0.001) and a negative correlation with creatinine clearance (rs = -0.50, P less than 0.01). 3. During infusion of alpha-hANP, although the urinary excretion of protein did not change significantly in the normal subjects, it increased from 0.6 +/- 0.2 to 3.0 +/- 0.8 mg min-1 m-2 (P less than 0.001) in the patients with glomerulonephritis. The urinary protein/creatinine ratio did not change significantly in the former (from 0.18 +/- 0.05 to 0.22 +/- 0.06; NS), whereas it rose from 3.25 +/- 0.94 to 7.62 +/- 1.31 (P less than 0.001) in the latter. 4. The urinary excretions of albumin and of alpha 1-, alpha 2-, beta- and gamma-globulins, which were electrophoretically analysed, all increased in eight nephrotic patients during or immediately after infusion of alpha-hANP.(ABSTRACT TRUNCATED AT 250 WORDS)