Rat brain natriuretic peptide. Isolation from rat heart and tissue distribution

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 peptide and 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 micrograms/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.