MECHANISMS OF ISOPROTERENOL-INDUCED ATRIAL-NATRIURETIC-PEPTIDE RELEASE FROM SUPERFUSED RABBIT ATRIA

The mechanisms for isoproterenol-induced atrial natriuretic peptide (ANP) release were studied in superfused rabbit sliced right atria. Addition of 1 muM norepinephrine to this preparation induced a significant monophasic twofold rise in ANP release. This effect was abolished by 1 muM propranolol and mimicked by 1 muM isoproterenol. Furthermore, addition of 200 muM 3-isobutyl-1-methylxanthine (IBMX) to the superfusing medium potentiated isoproterenol effect 31%. In addition, superfusion of slices with 0.5 mM N6,2-O-dibutyryladenosine 3',5'-cyclic monophosphate [(Bu)-2cAMP] enhanced ANP release in the same manner as the beta-agonist. After isoproterenol stimulation, adenosine 3',5'-cyclic monophosphate (cAMP) concentration in effluents increased significantly. ANP secretory response to isoproterenol was unaffected by extracellular calcium concentration or 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Finally, 10 muM indomethacin significantly reduced isoproterenol-stimulated ANP release. It is concluded that 1) norepinephrine-induced ANP release is mediated by its beta-agonist activity, 2) isoproterenol-stimulated release appears to be mediated by cAMP, 3) isoproterenol effect does not require extracellular calcium, and 4) prostaglandins may be involved in this beta-adrenergic effect.