Atrial natriuretic peptide (ANP) is a regulatory hormone widely expressed, along with its receptors, in organs and body tissues. ANP is well known to inhibit aldosterone secretion from mammalian adrenals, but its effect on glucocorticoid-hormone production is controversial. In vivo experiments showed that prolonged ANP administration raised the plasma concentration of cortisol in both normal and dexamethasone/captopril-treated guinea pigs (i.e. in animals with pharmacologically interrupted hypothalamic-pituitary-adrenal axis and renin-angiotensin system). ANP did not affect cortisol secretion from dispersed guinea pig zona fasciculata-reticularis cells, but enhanced catecholamine release from adrenomedullary cells. ANP stimulated cortisol output from guinea pig adrenal slices containing medullary chromaffin tissue, and the β-adrenoceptor antagonist l-alprenolol blocked this effect. The conclusion is drawn that ANP, when the structural integrity of the adrenal gland is preserved, is able to enhance glucocorticoid secretion in guinea pigs, through an indirect mechanism involving the rise in the catecholamine release, which in turn, acting in a paracrine manner, stimulate secretion of inner adrenocortical cells.

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