Ward L E, Hunter L W, Grabau C E, Tyce G M, Rorie D K
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
J Auton Nerv Syst. 1996 Dec 14;61(3):235-42. doi: 10.1016/s0165-1838(96)00089-6.
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.
在基础条件下，去甲肾上腺素、肾上腺素、多巴胺以及游离型和延伸型[甲硫]脑啡肽会自肾上腺自发流出。本研究旨在确定一氧化氮在这些流出过程中是否具有调节作用。用Krebs - Ringer溶液逆行灌注杂种狗的离体肾上腺（n = 63）。在一些实验中，向灌注液中加入一氧化氮合成抑制剂NG - 单甲基 - L - 精氨酸（3×10⁻⁴ M）。在其他实验中，加入一氧化氮供体之一，3 - 吗啉代硝酮（10⁻⁷ M或10⁻⁵ M）或硝普钠（10⁻⁶ M或10⁻⁴ M）。通过高效液相色谱 - 电化学检测法定量灌注液中的去甲肾上腺素、肾上腺素、多巴胺及其代谢产物3,4 - 二羟基苯乙二醇和3,4 - 二羟基苯乙酸，在一些实验中，通过放射免疫测定法测定[甲硫]脑啡肽。在存在NG - 单甲基 - L - 精氨酸的情况下，去甲肾上腺素、肾上腺素和多巴胺的基础流出量相对于对照显著增加，但游离型和延伸型[甲硫]脑啡肽的流出量未改变。在存在L - 精氨酸（10⁻³ M）的情况下，NG - 单甲基 - L - 精氨酸对儿茶酚胺流出的影响被逆转。硝普钠（10⁻⁶ M）抑制去甲肾上腺素和肾上腺素的流出，而3 - 吗啉代硝酮对这些流出无影响。多巴胺的流出似乎受与去甲肾上腺素和肾上腺素不同的控制，因为多巴胺的流出不受硝普钠影响，且3 - 吗啉代硝酮（10⁻⁷ M）会使其随时间减少。结论是，内源性产生的一氧化氮抑制离体狗肾上腺中去甲肾上腺素、肾上腺素和多巴胺的基础流出；这种抑制对去甲肾上腺素和肾上腺素似乎接近最大程度，但对多巴胺并非如此。
