NITRIC-OXIDE REDUCES BASAL EFFLUX OF CATECHOLAMINES FROM PERFUSED DOGADRENAL-GLANDS

Norepinephrine, epinephrine, dopamine, and both the free and extended forms of [met]enkephalin spontaneously efflux from adrenal glands unde r basal conditions. The present study was done to determine whether ni tric oxide has a regulatory role in these effluxes. Isolated adrenal g lands (n = 63) from mongrel dogs were perfused retrogradely with Krebs -Ringer solution. In some experiments N-G-monomethyl-L-arginine (3 X 1 0(-4) M), an inhibitor of nitric oxide synthesis, was added to the per fusate. In other experiments one of the nitric oxide donors, 3-morphol inosydnonimine (10(-7) M or 10(-5) M) or sodium nitroprusside (10(-6) M or 10(-4) M) was added. Norepinephrine, epinephrine, dopamine and th eir metabolites 3,4-dihydroxyphenylglycol and 3,4-dihydroxyphenylaceti c acid in perfusates were quantitated by high performance liquid chrom atography with electrochemical detection and in some experiments the [ met]enkephalins were determined by radioimmunoassay. In the presence o f N-G-monomethyl-L-arginine, the basal effluxes of norepinephrine, epi nephrine, and dopamine were significantly increased from control, but the effluxes of the free and extended forms of the [met]enkephalins we re not changed. The effects of N-G-monomethyl-L-arginine on catecholam ine efflux were reversed in the presence of L-arginine (10(-3) M). Sod ium nitroprusside (10(-6) M) inhibited effluxes of norepinephrine and epinephrine and 3-morpholinosydnonimine had no effect on these effluxe s. Dopamine efflux appeared to be under different controls from those of norepinephrine and epinephrine since dopamine efflux was unaffected by sodium nitroprusside and was decreased over time by 3-morpholinosy dnonimine (10(-7) M). It is concluded that endogenously produced nitri c oxide inhibits the basal efflux of norepinephrine, epinephrine, and dopamine from isolated dog adrenal glands; this inhibition appears to be near maximal for norepinephrine and epinephrine but not for dopamin e.