Long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide enhance the urinary excretion rate of beta2-microglobulin.

The atrial natriuretic peptide (ANP) gene synthesizes a 126-amino acid (aa) prohormone from which four peptide hormones are derived. These 4 peptide hormones consisting of aa 1 to 30 (ie, long-acting natriuretic peptide [LANP]), aa 31 to 67 (vessel dilator), aa 79 to 98 (kaliuretic peptide), and aa 99 to 126 (ie, ANP) have diuretic, natriuretic, and/or kaliuretic properties. ANP has been reported to have its natriuretic and protein-excreting effects via both the proximal and distal tubules, but where in the kidney the other three peptide hormones have their natriuretic and/or diuretic effects is unknown. Further, it has never been investigated as to whether these three other peptide hormones enhance protein excretion. The present investigation was designed to determine (1) if these atrial peptides enhance protein excretion and (2) if their effects involve the proximal tubules of healthy humans by examining the excretion rate of beta2-microglobulin, a marker of proximal tubule function. Twenty-four healthy human subjects were studied following the infusion of 100 ng/kg body weight/min for 60 minutes of each of the respective peptides. LANP enhanced the excretion rate of beta2-microglobulin 2-fold within 20 minutes of beginning its infusion (P < .05) and was 2.5-fold higher than the preinfusion excretion rate at the end of the infusion. The excretion rate of beta2-microglobulin continued to be significantly (P < .01) increased for 3 hours after cessation of the LANP infusion, with the maximal excretion rate (ie, 3.8-fold increase) at 2.5 hours after stopping the infusion. Vessel dilator showed a more marked enhancement of beta2-microglobulin during its infusion, with the excretion rate increasing 2.5-fold at 20 minutes, and was increased 4-fold (P < .01) at the end of the infusion. With cessation of the vessel dilator infusion, the excretion rate of beta2-microglobulin decreased but was still elevated 2-fold (P < .05) 3 hours after stopping the infusion. Kaliuretic peptide enhanced the beta2-microglobulin excretion rate a maximal 3-fold, which occurred at the end of its infusion. The beta2-microglobulin excretion secondary to kaliuretic peptide remained 2-fold (P < .05) above baseline during the 3-hour postinfusion period. These peptide hormones similarly enhanced the albumin and total protein excretion rates 2- to 4-fold. These results indicate that LANP, vessel dilator, and kaliuretic peptide each (1) enhance protein excretion in healthy humans and (2) inhibit proximal tubular protein reabsorption.