Site of the action of a synthetic atrial natriuretic peptide evaluated in humans

• Published in: Kidney international Vol. 32; no. 4; pp. 537 - 546
• Main Authors: Biollaz, Jérôme, Bidiville, Jacques, Diézi, Jacques, Waeber, Bernard, Nussberger, Jürg, Brunner–Ferber, Françoise, Gomez, Hector J., Brunner, Hans R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-10-1987; Nature Publishing
• Subjects: Adult; Atrial Natriuretic Factor - administration & dosage; Atrial Natriuretic Factor - pharmacology; Biological and medical sciences; Diuresis - drug effects; Eicosanoic Acids - administration & dosage; Eicosanoic Acids - pharmacology; Fundamental and applied biological sciences. Psychology; Glomerular Filtration Rate - drug effects; Humans; Infusions, Intravenous; Kidney Tubules - drug effects; Kidney Tubules, Distal - drug effects; Kidney Tubules, Distal - metabolism; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Lithium - pharmacokinetics; Lithium - urine; Male; Natriuresis - drug effects; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Renal Circulation - drug effects; Vertebrates: urinary system; Human; Urine; Glomerular filtration; Urinary system; Sodium; Peptide hormone; Nephron; Reabsorption; Clearance; Inorganic element; Atrial natriuretic factor; Kidney
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1987.242

Site of the action of a synthetic atrial natriuretic peptide evaluated in humans. The renal site of the natriuretic effect of human, atrial natriuretic peptide (hANP) was studied using clearance techniques in eight salt–loaded normal volunteers undergoing maximal water diuresis. Lithium was used as a marker of proximal sodium reabsorption. According to a two–way, single blind, crossover design, hANP (Met12-(3–28)-eicosahexapeptide, (2 µg/min) or its vehicle (Ve) were infused for two hours, followed by a two-hour recovery period. Blood pressure, heart rate and inulin clearance remained unchanged. During hANP infusion, the filtration fraction increased slightly from 19.6 to 24.3% (P < 0.001), fractional water excretion rose transiently at the beginning of the infusion. Fractional excretion of sodium increased markedly from 2.2% to 7.4% (P < 0.001) but remained unchanged with Ve. ANP increased fractional excretion of lithium slightly from 46 to 58% (P < 0.01), while it remained stable at 47% during Ve. The distal tubular rejection fraction of sodium calculated from sodium and lithium clearances rose markedly from 4.7 to 13% (P < 0.001) and returned to 6.2% at the end of the recovery period. Thus, under salt loading and water diuresis conditions, hANP infusion did not alter GFR, but reduced proximal reabsorption of sodium, and markedly enhanced the fraction of sodium escaping distal tubular reabsorption, suggesting that hANP-induced natriuresis is due, for an important part, to inhibition of sodium reabsorption in the distal nephron.