We have isolated a cardiac natriuretic peptide of 5,000 d from atrial tissues from 500 rats and determined its amino acid sequence. The 5,000 d atrial natriuretic factor was elucidated to be a 45 amino acid peptide with the sequence of
S-Q-D-S-A-F-R-I-Q-E-R-L-R-N-S-K-M-A-H-S-S-S-C-F-G-Q-K-I-D-R-I-G-A-V-S-R-L-G-C-D-G-L-R-L-F by sequencing the native peptideand its lysyl endopeptidase digests. The sequence of this peptide was identical to the amino acid sequence (51-95) of the rat brain natriuretic peptide precursor deduced from the complementary DNA (cDNA) sequence. The cardiac natriuretic peptide with a molecular weight of 5,000, or rat brain natriuretic peptide, was identified as the major storage form and as the sole secretory form derived from the brain natriuretic peptide precursor in the rat heart The rat brain natriuretic peptide level in the atrium was 3.68±0.61 /ig/g, which represents about 4% of that of atrial natriuretic factor. Rat brain natriuretic peptide was also detected in the ventricle. The ratio of brain natriuretic peptide to atrial natriuretic peptide in the ventricle was approximately 30% and much higher than that in the atrium. Rat brain natriuretic peptide, however, was not detectable in the brain. We conclude that the 5,000 d cardiac natriuretic peptide is rat brain natriuretic peptide with 45 amino acids derived from the brain natriuretic peptide precursor and is secreted from the rat heart as a novel cardiac hormone. (Hypertension 1990;15:774-778) B y using radioimmunoassay (RIA) for the ring structure of isoatriaJ natriuretic peptide (iso-ANP), which is the highly conserved sequence of natriuretic peptides, and radioreceptor assay for atrial natriuretic peptides (ANP), we have already demonstrated the presence of a considerable amount of a novel cardiac natriuretic peptide with a molecular weight of 5,000 in the rat atrium, which is distinct from iso-ANP and rat atrial natriuretic factor-(99-126) [rat ANP-(99-126)] isolated previously.