MODULATION OF HYPOTHALAMIC NOREPINEPHRINE RELEASE BY ATRIAL-NATRIURETIC-PEPTIDE - INVOLVEMENT OF CYCLIC-GMP

The ability of atrial natriuretic peptide (ANP) to modulate K+-stimulated release of [H-3]norepinephrine ([H-3]NE) from rat hypothalamic slices was investigated, ANP-(1-28) significantly decreased K+-stimulated [H-3]NE release in a concentration-dependent manner (maximal inhibition = 22% of control with 100 nM, ED50 = 70 pM). Pretreatment with pertussis toxin did not alter the response to ANP. 8Br-cGMP (10-mu-M), a cGMP analog, significantly decreased [H-3]NE release and when combined with 10 nM ANP-(1-28), an additive effect was observed. Additionally, 3-isobutyl 1-methylxanthine (IBMX) (200-mu-M), a phosphodiesterase inhibitor, combined with ANP-(1-28) 10 nM, significantly decreased [H-3]NE release. These results indicate that ANP-(1-28) modulated release of [H-3]NE from rat hypothalamic slices and the effect is most likely mediated by elevation of intraneuronal cGMP.