NATRIURETIC PEPTIDES AS CARDIAC HORMONES IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS - THE VENTRICLE IS A MAJOR SITE OF SYNTHESIS AND SECRETION OF BRAIN NATRIURETIC PEPTIDE

To study synthesis, storage, and secretion of brain natriuretic peptide (BNP) in the heart, we have measured BNP mRNA and BNP concentrations in the hearts of Wistar-Kyoto rats and also have investigated its secretion from the isolated perfused heart. The atrium expressed the BNP gene at a high level, and a considerable amount of BNP mRNA also was present in the ventricle, which corresponded to approximately 40% of the atrial BNP mRNA concentration. When tissue weight was taken into account, the total content of BNP mRNA in the ventricle was approximately threefold larger than that in the atrium, although the atrial natriuretic peptide (ANP) mRNA content in the ventricle was only 7% of that in the atrium. By contrast, the BNP concentration in the ventricle was 4.07 +/- 0.97 pmol/g, which was less than 1% of that in the atrium (451 +/- 86 pmol/g). The basal secretory rate of BNP from the isolated perfused whole heart was 49.3 +/- 6.1 fmol/min, approximately 60% of which was maintained even after atrial removal, whereas the secretory rate of ANP was reduced to less than 5%. We also studied age-matched spontaneously hypertensive rats-stroke prone. The rank order of the BNP mRNA concentration in the hearts of these rats was left ventricle > right ventricle > right atrium = left atrium, and the total BNP mRNA content and BNP secretory rate in the ventricle were twice as large as in Wistar-Kyoto rats. These results demonstrate that BNP is a novel cardiac hormone in rats and is predominantly synthesized in and secreted from the ventricle. This is in striking contrast to ANP, which occurs mainly in the atrium. The results also suggest possible pathophysiological roles of BNP in certain cardiovascular disorders.