The role of human atrial natriuretic peptide (alpha-hANP) in chronic blood pressure (BP) and extracellular fluid volume (ECFV) regulation remains elusive. Hence, the role of alpha-hANP in chronic renal failure is of particular interest since in this pathological condition: (1) increased sodium and water retention plays a major pathogenetic role in the development of hypertension and (2) altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. To evaluate the relationship between the degree of renal insufficiency, BP and circulating alpha-hANP, we determined plasma alpha-hANP concentrations by radioimmunoassay in 16 nondialyzed patients with progressive chronic renal failure (CRF) of various degrees; subsequently analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by means of gel permeation of plasma extracts from patients with CRF without concomitant hypertension. Serum creatinine concentrations ranged from 127 to 1187 (435 +/- 76) mumol/l, systolic BP from 135 to 200 (158 +/- 4) and diastolic BP from 80 to 110 (94 +/- 2) mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 (23 +/- 4) pmol/l which was thus significantly higher as compared to 9 +/- 2 pmol/l found in healthy volunteers (p less than 0.05). A highly significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92; p less than 0.01) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66) and serum creatinine concentration (r = 0.59), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)