Effect of low dose infusion of atrial natriuretic peptide on renal function in man

1988 ◽  
Vol 75 (4) ◽  
pp. 403-410 ◽  
Author(s):  
L. R. Solomon ◽  
J. C. Atherton ◽  
H. Bobinski ◽  
V. Hillier ◽  
R. Green
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Low Dose ◽  
Plasma Renin ◽  
Lithium Clearance ◽  
Plasma Aldosterone Concentration ◽  
Proximal Tubular Function ◽  
Small Change ◽  
Magnesium Excretion ◽  
Atrial Natriuretic

1. The effects of the infusion of a low dose (2 pmol min−1 kg−1 for 3 h) of human atrial natriuretic peptide (hANP) were studied in seven healthy volunteers undergoing a water diuresis. Lithium clearance was used to monitor proximal tubular function. 2. hANP increased urine flow rate, sodium, calcium and magnesium excretion without significant changes in potassium and phosphate excretion, heart rate or blood pressure. 3. hANP caused a small change in fractional lithium clearance, and larger changes in distal nephron handling of sodium and water. 4. Plasma renin activity tended to decrease during the infusion of hANP, while plasma aldosterone concentration decreased during and increased after stopping the infusion of hANP. 5. The data suggest that hANP inhibits the reabsorption of sodium and water by an action on distal segments of the nephron and perhaps the proximal tubule. Inhibition of renin and aldosterone secretion may contribute to the natriuresis.

Low-Dose Brain Natriuretic Peptide Infusion in Normal Men and the Influence of Endopeptidase Inhibition

1997 ◽  
Vol 92 (3) ◽  
pp. 255-260 ◽  
Author(s):  
C. M. Florkowski ◽  
A. M. Richards ◽  
E. A. Espiner ◽  
T. G. Yandle ◽  
E. Sybertz ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Plasma Renin Activity ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Low Dose ◽  
Plasma Renin ◽  
Renin Activity ◽  
Plasma Brain Natriuretic Peptide ◽  
Normal Men ◽  
Atrial Natriuretic

1. To assess the threshold dose for bioactivity of brain natriuretic peptide and the role of endopeptidase 24.11 in metabolism of brain natriuretic peptide at physiological plasma levels, we studied eight normal men receiving 2 h infusions of low-dose brain natriuretic peptide [0.25 and 0.5 pmol min−1 kg−1 with and without pretreatment with an endopeptidase inhibitor (SCH 32615, 250 mg intravenously)] in placebo-controlled studies. 2. Plasma brain natriuretic peptide increased 2-fold during the infusion of 0.25 pmol min−1 kg−1 (mean increment above control 3.9 pmol/l, P < 0.001), and tripled (P < 0.001) with 0.5 pmol min−1 kg−1. Plasma renin activity was inhibited by both doses (14.8%, P < 0.01, and 20%, P < 0.001, respectively). A significant natriuresis (56% increase in urine sodium/creatinine ratio, P < 0.02) occurred with the higher dose. Blood pressure, haematocrit, plasma cGMP, atrial natriuretic peptide and aldosterone were unaffected by either dose. 3. Compared with brain natriuretic peptide (0.5 pmol min−1 kg−1) alone, SCH 32615 pretreatment increased peak plasma brain natriuretic peptide (13.4±0.78 versus 12.4±0.86 pmol/l, P < 0.05), ANP (7.5±0.96 versus 5.9±0.4 pmol/l, P < 0.01) and cGMP (4.8 ± 1.7 versus 3.9 ± 1.4 nmol/l, P < 0.001). Plasma renin activity was further suppressed with SCH 32615 pretreatment (29% compared with 20%, P < 0.001). 4. Small acute increments in plasma brain natriuretic peptide (4 pmol/l) have significant biological effects in normal men without altering plasma atrial natriuretic peptide or cGMP.

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

1987 ◽  
Vol 72 (3) ◽  
pp. 305-312 ◽  
Author(s):  
J. V. Anderson ◽  
J. Donckier ◽  
N. N. Payne ◽  
J. Beacham ◽  
J. D. H. Slater ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Natriuretic Hormone ◽  
Plasma Aldosterone Concentration ◽  
Water Excretion ◽  
Physiological Range ◽  
Atrial Natriuretic

1. 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. 2. We infused human α-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. 3. The infusion of ANP caused a 60% increase of mean urinary sodium excretion from 111 ± 18 to 182 ± 30 μmol/min (P < 0.001) and a 28% increase of mean water excretion from 10.8 ± 0.8 to 13.8 ± 1.6 ml/min (P < 0.01). 4. 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 < 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. 5. No significant change in any of the variables mentioned above occurred during the infusion of the vehicle alone on a separate study day. 6. The demonstration that recreation of plasma concentrations of ANP within the physiological range by intravenous infusion induces a natriuresis provides new evidence supporting the role of ANP as a natriuretic hormone.

Effect of physical exercise in hypobaric conditions on atrial natriuretic peptide secretion

1992 ◽  
Vol 263 (3) ◽  
pp. R647-R652 ◽  
Author(s):  
O. Vuolteenaho ◽  
P. Koistinen ◽  
V. Martikkala ◽  
T. Takala ◽  
J. Leppaluoto
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Sea Level ◽  
Natriuretic Peptide ◽  
Plasma Renin ◽  
Amino Terminal ◽  
Significant Difference ◽  
Elimination Mechanism ◽  
Peptide Secretion ◽  
Ergometer Test ◽  
Atrial Natriuretic

To evaluate the role of atrial natriuretic peptide (ANP) in exercise-related cardiovascular and hormonal adjustments in hypobaric conditions, 14 young athletes performed a maximal ergometer test in a hypobaric chamber adjusted to simulate the altitudes of sea level and 3,000 m. Plasma immunoreactive ANP levels rose from 5.89 to 35.1 pmol/l at sea level and rose significantly less (P less than 0.05), from 5.36 to 22.3 pmol/l, at simulated 3,000 m. Plasma immunoreactive amino-terminal peptide of proANP (NT-proANP) levels increased to the same extent at sea level and at simulated 3,000 m (from 240 to 481 pmol/l and from 257 to 539 pmol/l, respectively). Plasma immunoreactive aldosterone increased significantly less at simulated 3,000 m (P less than 0.05), but the changes in plasma renin were similar in both conditions. Plasma immunoreactive endothelin-1 and serum erythropoietin levels remained unchanged. In conclusion, we found a blunted ANP response to maximal exercise of ANP in acute hypobaric exposure compared with that in normobaric conditions, but no significant difference in the NT-proANP responses between the two conditions. The divergence may be due to stimulation of the elimination mechanism of ANP.

Effect of a meal containing protein on lithium clearance and plasma immunoreactive atrial natriuretic peptide in man

1988 ◽  
Vol 75 (2) ◽  
pp. 151-157 ◽  
Author(s):  
L. R. Solomon ◽  
J. C. Atherton ◽  
H. Bobinski ◽  
S. L. Cottam ◽  
C. Gray ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Protein Content ◽  
Natriuretic Peptide ◽  
Proximal Tubules ◽  
High Protein ◽  
Lithium Clearance ◽  
Protein Meal ◽  
Low Protein ◽  
High Protein Meal ◽  
Atrial Natriuretic

1. The effect of meals with a high and low protein content and of the fasting state on renal function and plasma atrial natriuretic peptide was studied in water-loaded normal volunteers. 2. Creatinine clearance increased after the high protein meal, but did not change after the low protein meal or while fasting. Observations of similar increases in urine sodium and potassium excretion and a transient decrease in urine flow after both meals suggest that the protein content of the meal is not an important contributory factor in these responses to feeding. 3. Absolute delivery of sodium and water out of the proximal tubules (assessed by the lithium clearance method) was higher after both meals than while fasting; fractional lithium clearance was higher after the low protein meal than the high protein meal and while fasting. Absolute reabsorption from proximal tubules was increased after only the high protein meal. 4. A transient decrease in the fraction of water delivered to distal nephron segments that appeared in the urine (fractional distal water excretion) was observed after both meals. Fractional distal sodium excretion and absolute distal sodium and water reabsorption increased after both meals. 5. Since plasma atrial natriuretic peptide either decreased (high protein meal) or remained unchanged (low protein meal and fasting), it is unlikely that this hormone is involved in the hyperfiltration after the high protein meal and the natriuresis after both high and low protein meals.

Assessment of atrial natriuretic peptide resistance in cirrhosis with head-out water immersion and atrial natriuretic peptide infusion

1993 ◽  
Vol 71 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Louis Legault ◽  
Leonard C. Warner ◽  
Wai Ming Leung ◽  
Alexander G. Logan ◽  
Laurence M. Blendis ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Collecting Duct ◽  
Water Immersion ◽  
Plasma Renin ◽  
Sodium Balance ◽  
Plasma Sodium ◽  
Sodium Retention ◽  
Serum Aldosterone ◽  
Atrial Natriuretic

The nature of sodium retention in cirrhosis complicated by ascites has been studied for the last 30 years. Resistance to the natriuretic action of atrial natriuretic peptide (ANP) may play a potential role in this sodium retention. To further evaluate this possibility, we studied 12 patients with biopsy-proven cirrhosis and ascites on 2 consecutive days after a 7-day period off diuretics while receiving a 20 mmol/day sodium restricted diet. Following a crossover design, patients underwent head-out water immersion (HWI) for 3 h and were infused with a α-human ANP for 2 h on 2 consecutive days. Blood and urine samples were collected hourly. Five patients displayed a natriuretic response to HWI, sufficient to achieve negative sodium balance, and these patients were termed responders. Each of these five patients also displayed a natriuretic response to ANP infusion. In contrast, the other seven patients (nonresponders) consistently failed to develop a natriuretic response to either maneuver. The two groups had similar elevations in plasma ANP concentrations, but at baseline differed in terms of plasma sodium, plasma renin activity, and serum aldosterone. Despite higher serum aldosterone concentrations, nonresponders excreted less potassium than responders during the peak effect of the interventions, suggesting greater sodium delivery to the aldosterone-sensitive nephron segment in responders. We conclude that the inability to mount an adequate sodium excretory response to HWI in patients with cirrhosis may be conveyed through increased antinatriuretic factors that decrease the sodium delivery to the medullary collecting duct and inhibit the natriuretic effect of ANP at that site.Key words: atrial natriuretic peptide, cirrhosis, ascites, sodium.

Hemodynamic and renal effects of low-dose infusions of atrial peptide in awake dogs

1988 ◽  
Vol 254 (2) ◽  
pp. R161-R169 ◽  
Author(s):  
P. Bie ◽  
B. C. Wang ◽  
R. J. Leadley ◽  
K. L. Goetz
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Plasma Renin ◽  
Urine Flow ◽  
Right Atrial ◽  
Experimental Protocols ◽  
Cardiac Filling ◽  
Left And Right ◽  
Atrial Natriuretic

The effects of alpha-human atrial natriuretic peptide (alpha-hANP) on cardiovascular and renal function in conscious dogs were evaluated in two experimental protocols. In one protocol, alpha-hANP was infused intravenously at increasing rates of 50, 100, and 200 ng.min-1.kg-1 (stepup infusion) during successive 20-min periods. The greatest responses occurred during the final 20-min period of the stepup infusion when the plasma concentration of immunoreactive atrial natriuretic peptide (irANP) was increased by 44-fold over preinfusion values; pressures in the aorta and both atria were decreased at this time, whereas glomerular filtration rate, urine flow, and sodium excretion were increased. In a second protocol, alpha-hANP was infused for 1 h at constant rates of either 12.5, 25, or 50 ng.min-1.kg-1; these constant infusions increased plasma irANP by 3-, 7-, and 12-fold, respectively. Each infusion rate decreased left and right atrial pressures and increased urine flow and sodium excretion. The two lowest infusion rates elevated plasma irANP to levels that would be expected to occur only during unusual physiological, or perhaps pathophysiological, conditions. The two highest infusion rates decreased plasma renin activity. Nevertheless, the accompanying maximal increases in sodium excretion were modest (41-72%). These data imply that small changes in circulating atrial peptides that presumably occur under normal physiological conditions would not have a dominant effect on the regulation of sodium excretion; the peptides may, however, play a modulatory role on sodium excretion under these conditions. It remains to be determined whether the ability of atrial peptides to lower cardiac filling pressures is of physiological significance.

Atrial natriuretic peptide receptors in renal papilla of DOCA-salt hypertensive rats

1990 ◽  
Vol 259 (1) ◽  
pp. F130-F137
Author(s):  
E. Nuglozeh ◽  
G. Gauquelin ◽  
R. Garcia ◽  
J. Tremblay ◽  
E. L. Schiffrin
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Plasma Renin ◽  
Renal Papilla ◽  
Hypertensive Rats ◽  
Reducing Conditions ◽  
Anp Receptors ◽  
Atrial Natriuretic

The receptor for atrial natriuretic peptide (ANP) in the rat renal papilla was characterized pharmacologically. After solubilization and irreversible binding with disuccinimidylsuberate, it was shown on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) to be made of a single peptide of 125 kDa. The regulation of the renal papillary ANP receptor was studied in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats had suppressed plasma renin activity and increased plasma ANP concentrations (408 +/- 35 vs. 133 +/- 12 pg/ml in uninephrectomized controls, P less than 0.01). The renal papilla was hypertrophied in DOCA-salt hypertensive rats (93 +/- 1 vs. 52 +/- 1 mg, P less than 0.01). The density of ANP sites in the papilla was significantly higher in DOCA-salt rats (141 +/- 31 fmol/papilla) than in controls (34 +/- 8 fmol/papilla, P less than 0.01). Affinity of sites in DOCA-salt rats and controls was similar. The production of guanosine 3',5'-cyclic monophosphate (cGMP) in renal papilla in response to ANP was significantly higher in DOCA-salt rats. In contrast to the renal papillary ANP receptor, acid-washed vascular and glomerular ANP sites were significantly decreased in density in DOCA-salt hypertensive rats. In blood vessels and glomeruli, both the high- and low-molecular mass receptor (as detected on SDS-PAGE under reducing conditions) was proportionately decreased in density in DOCA-salt hypertensive rats. The present results suggest that an increased number of ANP receptors and exaggerated cGMP response to ANP in the renal papilla may underlie the increased natriuretic responsiveness of the kidney to ANP in DOCA-salt hypertensive rats.

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