The presence and molecular forms of cardiodilatin immunoreactivity in the human and rat right atrium

Abstract

A sensitive and specific radioimmunoassay has been developed for cardiodilatin; the N-terrninal peptide sequence of the atrial natriuretic peptide (ANP) prohorrnone. Cardiodilatin-immunoreactivity (-IR) concentrations in the human right atrial appendage we re found to correlate with ANP-IR concentrations, deterrnined by an established radioimmunoassay, (cardiodilatin-IR = 13.2 ± 1.2 nmoljg, ANP-IR = 19.8 ± 2.0 nmoljg, r = 0.80, p < 0.001). Characterisation of the cardiodilatin-IR in the human and rat right atrium by gel permeation and fast protein liquid chromatography revealed only two cardiodilatin-IR molecular forms. The larger more hydrophobic form, the majority of the cardiodÜatin-IR, contained in addition ANP-IR and therefore represents the prohorrnone. The smaller, less hydrophobic form, lacked ANP-IR and thus represents the cleaved N-terrninal peptide sequence of the prohorrnone. These findings indicate that the prohorrnone is the major molecular form in the human and rat atrium. Furthermore, they demonstrl:lte that a single large N-terrninal peptide, cardiodilatin, derived from the prohorrnone, may exist as a distinct molecular form in the atrium of these species.

Novel Chemiluminescent Enzyme Immunoassays for Individual Quantification of 3 Endogenous Molecular Forms of Atrial Natriuretic Peptide in Human Plasma

“…In contrast to the proANP/total ANP ratio of approximately 2.5% in healthy subjects, ADHF pa- tients exhibited a proANP ratio of approximately 12% at admission, which was consistent with the values observed in plasma of severe HF patients (22,33). The increased proANP/total ANP ratio in HF reflects an aberrant ratio of unprocessed proANP and mature α-ANP.…”

“…In the plasma, proANP is more resistant to protease digestion than α-ANP and thus more stably present (21). In addition, the aggregation of proANP observed in atrial tissues (31,32) is unlikely to occur in plasma, as indicated by chromatographic analyses (22,33). In this context, a possible influence of proANP aggregation on Ab detection is excluded when this CLEIA is used with plasma samples.…”

Molecular forms of natriuretic peptides in heart failure and their implications

“…Hunter et al 12 revealed that in patients with HF (functional class unspecified), pro-ANP was the predominant form. In three other studies, on the other hand, ANP appeared to be the major form in plasma samples from patients with HF 11 19 20. The difference may reflect the disease state of the patients from whom samples were collected.…”