Immunoreactive N-terminal fragment of proatrial natriuretic peptide, ANP (1–98), in plasma of healthy dogs and dogs with impaired volume regulation: a comparison with the C-terminal ANP (99–126)

Abstract

Atrial natriuretic peptide (ANP) is stored in atrial myocytes as a 126 amino acid precursor molecule ( ANP 1–126) and is cleaved during its release into circulation into the biologically active C-terminal ANP (99–126) and the N-terminal counterpart, ANP (1–98). While interest has focused on ANP (99–126) under physiological and path ophysiological conditions, data for the cosecreted N-terminal sequence, ANP (1–98) are generally missing. Plasma levels of the N-terminal immunoreactive peptide (N- ANP [1–98]) were measured in normal dogs, and in dogs with impaired volume regulation (congestive heart failure; chronic renal failure or Cushing's syndrome and compared with those of C- ANP (99–126). The N- ANP (1–98) concentration was 593· 1 ± 81·1 fmol ml −1 in normal subjects, which is about 60-fold higher than the C- ANP (99–126) (10·8 ± 2·6 fmol ml −1). In patients suffering from chronic renal failure ANP (1–98) was increased to 1582 ± 196 fmol ml −1, and in dogs with congestive heart failure to 1612 ± 244 fmol ml −1. In contrast, Cushing's syndrome dogs showed decreased N-ANP (1–98) concentrations (351 ± 65·9 fmol ml −1). There was a positive correlation between plasma levels of N- ANP (1–98) and C- ANP (99–126) levels (correlation coefficients: normal: r =0 · 78; congestive heart failure: r=0·76; chronic renal failure: r=0·86; Cushing's syndrome: r=0·57). High pressure liquid chromatographic analysis of dog plasma showed one major peak of N-terminal immunoreactivity corresponding to ANP (1–98). It is concluded that both the N-terminal fragment of the ANP prohormone, ANP (1–98), as well as the C-terminal sequence, ANP (99–126), change in parallel and, thus, may provide information on the pathophysiology of patients suffering from volume overload.