Increased adrenal medullary atrial natriuretic polypeptide synthesis in patients with primary aldosteronism

The present study was designed to determine whether atrial natriuretic polypeptide (ANP) is synthesized in the human adrenal gland and, if so, to investigate the ANP content of adrenal tissue and the ANP mRNA changes in patients with primary aldosteronism. A considerable amount of human alpha ANP-like immunoreactive substances was extracted from the remnant adrenal glands of three patients with primary aldosteronism (1.44, 1.0, and 0.77 pmol/g wet tissue; mean +/- SD, 1.07 +/- 0.28 pmol/g) and the adrenal glands of three kidney donors for transplantation (0.93, 0.58, and 0.27 pmol/g wet tissue; mean +/- SD, 0.59 +/- 0.27 pmol/g). High performance gel permeation chromatographic analysis coupled with a RIA of the tissue extract showed that the molecular form of ANP in the adrenal gland was the precursor form, i.e. human gamma ANP. An in situ hybridization study using an ANP cRNA probe indicated that the ANP mRNA was localized mainly in the medullary area of the gland. Northern blot analysis, using ANP cDNA as a probe, detected ANP mRNA in the adrenal gland. Furthermore, the level of ANP mRNA in the adrenal glands of patients with primary aldosteronism was obviously elevated compared to that in the kidney donors. Our results were the first to indicate that ANP is synthesized in the human adrenal medulla, and such medullary ANP synthesis increases in patients with hypermineralocorticoidism. These facts support the proposal that extraatrial (medullary) ANP synthesis might act in a paracrine or endocrine manner to regulate water and electrolyte homeostasis.