Nitric oxide reduces basal efflux of catecholamines from perfused dog adrenal glands.
Norepinephrine, epinephrine, dopamine, and both the free and extended forms of [met]enkephalin spontaneously efflux from adrenal glands under basal conditions. The present study was done to determine whether nitric oxide has a regulatory role in these effluxes. Isolated adrenal glands (n = 63) from mongrel dogs were perfused retrogradely with Krebs-Ringer solution. In some experiments NG-monomethyl-L-arginine (3 x 10(-4) M), an inhibitor of nitric oxide synthesis, was added to the perfusate. In other experiments one of the nitric oxide donors, 3-morpholinosydnonimine (10(-7) M or 10(-5) M) or sodium nitroprusside (10(-6) M or 10(-4) M) was added. Norepinephrine, epinephrine, dopamine and their metabolites 3,4-dihydroxyphenylglycol and 3,4-dihydroxyphenylacetic acid in perfusates were quantitated by high performance liquid chromatography with electrochemical detection and in some experiments the [met]enkephalins were determined by radioimmunoassay. In the presence of NG-monomethyl-L-arginine, the basal effluxes of norepinephrine, epinephrine, and dopamine were significantly increased from control, but the effluxes of the free and extended forms of the [met]enkephalins were not changed. The effects of NG-monomethyl-L-arginine on catecholamine efflux were reversed in the presence of L-arginine (10(-3) M). Sodium nitroprusside (10(-6) M) inhibited effluxes of norepinephrine and epinephrine and 3-morpholinosydnonimine had no effect on these effluxes. 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-morpholinosydnonimine (10(-7) M). It is concluded that endogenously produced nitric 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 dopamine.
Ward
L E
LE
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Hunter
L W
LW
Grabau
C E
CE
Tyce
G M
GM
Rorie
D K
DK
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004285:Dogs; D004744:Enkephalin, Methionine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002395:Catecholamines; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004744:Enkephalin, Methionine; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase