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作为细胞间通讯的串扰因子具有重要作用。本研究的目的是探讨整合自主神经功能和内分泌的神经内分泌系统的生理作用。在离体大鼠视上核（SON）的膜片钳记录表明，抑制性突触后电流的应用NO供体增加。对于伤害性刺激，将福尔马林（5%）或盐水皮下（s.c.）植入大鼠的双侧后爪。脑室旁核（PVN）神经元型一氧化氮合酶（nNOS）基因表达在s.c.注射福尔马林的大鼠与未处理的和注射盐水的大鼠相比。禁食2d可引起大鼠下丘脑室旁核和视上核nNOS基因表达下调。瘦素的中央管理防止食物剥夺引起的下调。高盐饮食组大鼠下丘脑室旁核和视上核nNOSmRNA和NADPH-d活性均高于高盐饮食组大鼠，高盐饮食组大鼠下丘脑室旁核和视上核nNOSmRNA和NADPH-d活性均高于高盐饮食组大鼠。从高盐饮食开始后2周开始，将抗高血压药物尼卡地平或卡托普利给予Dahl S大鼠2周。给予高盐饮食的Dahl S大鼠的PVN和SON中的nNOS mRNA不被尼卡地平治疗上调，而在盐负荷的Dahl S大鼠中的nNOS mRNA被卡托普利治疗上调至大于没有抗高血压药物。这些结果表明，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.