Long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide enhance the urinary excretion rate of beta(2)-microglobulin

The atrial natriuretic peptide (ANP) gene synthesizes a 126-amino acid (aa) prohormone from which four peptide hormones are derived. These 4 peptide h ormones consisting of aa 1 to 30 lie, 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 propertie s. ANP has been reported to have its natriuretic and protein-excreting effe cts via both the proximal and distal tubules, but where in the kidney the o ther three peptide hormones have their natriuretic and/or diuretic effects is unknown. Further, it has never been investigated as to whether these thr ee other peptide hormones enhance protein excretion. The present investigat ion 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 Pz-microglobulin, a marker of pro ximal tubule function. Twenty-four healthy human subjects were studied foll owing the infusion of 100 ng/kg body weight/min for 60 minutes of each of t he respective peptides. LANP enhanced the excretion rate of beta (2)-microg lobulin 2-fold within 20 minutes of beginning its infusion (P < .05) and wa s 2.5-fold higher than the preinfusion excretion rate at the end of the inf usion. The excretion rate of Pn-microglobulin continued to be significantly (P < .01) increased for 3 hours after cessation of the LANP infusion, with the maximal excretion rate lie, 3.8-fold increase) at 2.5 hours after stop ping the infusion. Vessel dilator showed a more marked enhancement of pp-mi croglobulin during its infusion, with the excretion rate increasing 2.5-fol d at 20 minutes, and was increased 4-fold (P < .01) at the end of the infus ion. With cessation of the vessel dilator infusion, the excretion rate of b eta (2)-microglobulin decreased but was still elevated 2-fold (P < .05) 3 h ours after stopping the infusion. Kaliuretic peptide enhanced the beta (2)- microglobulin excretion rate a maximal I-fold, which occurred at the end of its infusion. The beta (2)-microglobulin excretion secondary to kaliuretic peptide remained P-fold (P < .05) above baseline during the 8 hour postinf usion period. These peptide hormones similarly enhanced the albumin and tot al protein excretion rates 2- to 4-fold. These results indicate that LANP, vessel dilator, and kaliuretic peptide each (1) enhance protein excretion i n healthy humans and (2) inhibit proximal tubular protein reabsorption. Cop yright (C) 2000 by W.B. Saunders Company.