CORTICOID REGULATION OF ATRIAL-NATRIURETIC-FACTOR SECRETION AND GENE-EXPRESSION

This study investigated the acute effects of glucocorticoids and mineralocorticoids on atrial natriuretic factor (ANF) biosynthesis in vivo. Groups of male Sprague-Dawley rats were injected with 1 mg dexamethasone (Dex), 10 mg deoxycorticosterone acetate (DOCA) or vehicle alone. Different groups were studied after periods of 30 min to 8 h. Plasma and left atrial ANF concentrations and ANF mRNA levels were measured 2-8 h after corticoid injection. From 30 min to 2 h after injection, ANF mRNA was analyzed by quantitative and qualitative assessments. There was a two- to threefold increase in plasma levels of ANF in Dex-treated rats compared with controls at all time periods (P < 0.05). Although ANF plasma levels increased over time following DOCA treatment, they were not significantly different from control values. Dex treatment also increased normalized ANF mRNA levels 77% above control levels during the first 4 h after injection (P < 0.05). Thereafter there was a return of mRNA levels to that seen in controls. There was no qualitative difference in the ANF mRNA at any time as assessed by Northern hybridization. In contrast, DOCA increased ANF mRNA levels only after 8 h (P < 0.05). No significant changes in left atrial ANF content were noted during this study. In a separate study, Dex was administered to isolated left atria in vitro in a superfusion system. Superfusion with 2 X 10(-5) M Dex produced a 40% increase in ANF secretory rate within 20 min (P = 0.036). We conclude that Dex induces a direct rapid increase in ANF mRNA levels and ANF secretion in rats. DOCA increases ANF secretion but the effect is delayed and is likely to be mediated through a primary effect on volume expansion.