A role of NO on neuroendocrine system : molecular, pharmacological and neurophysiological approaches

NO被认为不仅在外周系统，而且在中枢神经系统中都作为细胞间通讯的串扰因子发挥重要作用。本研究的目的是检测神经内分泌系统的生理作用，该系统整合了自主神经功能和内分泌。大鼠视上核(SON)膜片钳记录显示，NO供体可增加突触后抑制性电流。对于伤害性刺激，皮下注射福尔马林(5%)或生理盐水(Sc)。进入大鼠的双侧后爪。下丘脑室旁核(PVN)神经元一氧化氮合酶(NNOS)基因表达在sc后2 h和6 h显著增加。注射福尔马林与未经处理和注射生理盐水的大鼠进行比较。禁食2d后，下丘脑室旁核和SON中nNOS基因表达下调。中央给药的瘦素阻止了食物匮乏导致的这种下调。在锂诱导的尿崩症大鼠，PVN和SON的nNOS mRNA和NADPH-黄递酶活性均升高，高血压达尔-S大鼠的PVN和SON的nNOS-mRNA和NADPH-黄递酶活性高于高盐饮食的Dahl-R大鼠。达尔S大鼠在开始高盐饮食后2周开始给药，尼卡地平或卡托普利，为期2周。尼卡地平对高盐饮食达尔-S大鼠下丘脑室旁核和SON中nNOS mRNA表达无明显影响，而盐负荷达尔-S大鼠经卡托普利治疗后，nNOSm RNA表达明显上调，且显著高于未用药组。这些结果提示，NO在神经内分泌系统中可能具有多种生理作用。

NO is thought to have important roles as a factor of cross-talk with cell-to-cell communication in not only peripheral system but also central nervous system. The purpose of the present study was to examine the physiological role on the neuroendocrine system that integrates autonomic nervous function and endocrine. Patch-clamp recording from the rat supraoptic nucleus (SON) in vitro demonstrated that inhibitory postsynaptic currents were increased by application of NO donor. For nociceptive stimulation, formalin (5%) or saline was injected subcutaneously (s.c.) into the bilateral hind paws of rats. The expression of the neuronal NO synthase (nNOS) gene in the paraventricular nucleus (PVN) was significantly increased 2 and 6 h after s.c. injection of formalin in comparison with that in untreated and saline injected rats. Food deprivation for 2 days caused downregulation of the expression of the nNOS gene in the PVN and the SON of rats. Central administration of leptin prevented food deprivation-induced that downregulation. In lithium-induced diabetes insipidus rats nNOS mRNA and NADPH-diaphorase activity were increased in the PVN and the SON.The levels of nNOS mRNA and NADPH-diaphorase activity in the PVN and SON of hypertensive Dahl S rats were greater than those in Dahl R rats on a high salt diet. The antihypertensive drugs, either nicardipine or captopril were administered to the Dahl S rats for 2 weeks beginning at 2 weeks after the start of the high salt diet. The nNOS mRNA in the PVN and SON of Dahl S rats given a high salt diet was not upregulated by treatment with nicardipine, while the nNOS mRNA in salt-loaded Dahl S rats was greater upregulated by treatment with captopril to a greater than without the antihypertensive drug. These results suggest that NO may have various physiological roles in the neuroendocrine system.