C-TYPE NATRIURETIC PEPTIDE AS A POSSIBLE LOCAL MODULATOR OF ALDOSTERONE SECRETION IN BOVINE ADRENAL ZONA GLOMERULOSA

Although atrial and brain natriuretic peptides are well known to be in volved in the regulation of cardiovascular and endocrine functions as circulating hormones, the roles of the C-type natriuretic peptide (CNP ) remain unknown. We examined the effects of CNP on the secretion of a ldosterone and cyclic nucleotides from bovine adrenal zona glomerulosa cells in culture. CNP produced a dose-dependent increase in the basal secretion of cGMP, with an EC(50) of 3.8 x 10(-10) M. CNP significant ly inhibited the ACTH-induced increase in aldosterone and cAMP in a do se-related manner, with an IC50 of 3.6 x 10(-10) M. Although ACTH itse lf did not increase cGMP secretion, the addition of CNP elicited a sig nificant increase in cGMP secretion. The effects of CNP on the basal s ecretion of cGMP and the ACTH-induced secretion of aldosterone were si gnificantly reversed by a nonpeptide natriuretic peptide receptor anta gonist, HS-142-1. CNP immunoreactivity was localized in the zona glome rulosa by immunohistochemical staining. In addition, expression of CNP messenger RNA and natriuretic peptide B receptor messenger RNA was de monstrated by RT-PCR in the zona glomerulosa tissue and cells in cultu re. These findings suggest that CNP is a local factor regulating ACTH- induced aldosterone secretion through a guanylyl cyclase-cGMP pathway.