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

一氧化氮被认为不仅在外周系统，而且在中枢神经系统中作为细胞间通讯的串扰因子发挥着重要作用。本研究的目的是研究其对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。膜片钳对大鼠视上核（SON）的体外记录显示，NO供体增加了抑制性突触后电流。大鼠双侧后爪皮下注射5%福尔马林或生理盐水进行伤害性刺激。大鼠室旁核（PVN）神经元NO合成酶（nNOS）基因在s.c.注射福尔马林后2和6 h的表达均较未注射和生理盐水组显著升高。剥夺食物2 d后，大鼠PVN和SON中nNOS基因表达下调。瘦素的集中管理防止了食物匮乏引起的下调。锂诱导尿崩症大鼠PVN和SON中nNOS mRNA和NADPH-diaphorase活性升高。高血压达尔S大鼠PVN和SON中nNOS mRNA水平和NADPH-diaphorase活性均高于高盐饮食达尔R大鼠。从高盐饮食开始后2周开始，给予达尔S大鼠2周的降压药物尼卡地平或卡托普利。高盐饮食组达尔S大鼠PVN和SON的nNOS mRNA未被硝地平上调，而高盐饮食组达尔S大鼠卡托普利组nNOS mRNA的上调幅度大于未加卡托普利组。这些结果提示NO可能在神经内分泌系统中具有多种生理作用。

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.