Abstract
To clarify the molecular nature and dynamics of circulating a human atrial natriuretic polypeptide (αhANP) in chronic renal disease, the plasma concentrations of αhANP were determined by radioimmunoassays using two distinct monoclonal antibodies (MoAbs). One MoAb (10B1) recognized N-terminus of αhANP, while the other (C351) recognized the ring structure. The preliminary studies revealed a close correlation (r=0.97, p<0.0001) between plasma αhANP measured with 10B1 and C351 MoAbs, supporting the theory that the main circulating form is αhANP (1-28). Therefore, the more sensitive radioimmunoassay using MoAb (C351) was used in the present studies. The plasma αhANP was 3.8 ± 1.7 (mean ± SD) in healthy subjects, 2.7 ± 1.4 fmol/ml in patients with chronic glomerulonephritis without renal failure, 16.2 ± 16.8 fmol/ml in patients with chronic renal failure, and 24.3 ± 10.5 fmol/ml in patients under maintenance hemodialysis. Thus, the elevation of plasma αhANP was related to the stages of renal damage. Although the plasma αhANP in 18 patients under maintenance hemodialysis declined significantly (p<0.01) after hemodialysis, their levels (17.9 ± 9.0 fmol/ml) after hemodialysis were still higher than those in healthy subjects. On the other hand, a positive correlation (r=0.65, p<0.05) between αhANP and creatinine in blood was found only in the group of chronic renal failure before maintenance hemodialysis. These results suggest that an impaired metabolism of αhANP in the kidney might play an important role in the elevation of plasma αhANP as well as the stimulation of αhANP secretion caused by the expansion of extracellular fluid.
