Terrell Mary Lee, Salas Nilson, Bui V, Summy-Long J Y, Kadekaro M
Department of Surgery, Division of Neurosurgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-0517, USA.
Exp Neurol. 2003 Dec;184(2):846-56. doi: 10.1016/S0014-4886(03)00305-4.
Our objective was to test the hypothesis that the cGMP signal-transduction mechanism mediates nitric oxide's (NO) modulation of oxytocin (OT) and vasopressin (VP) secretion from the hypothalamo-neurohypophysial system. Three studies were conducted in adult male Sprague-Dawley rats: (1a) Euhydrated rats received an intracerebroventricular (icv) infusion (1 microl/min for 30 min) of artificial cerebrospinal fluid (aCSF), vehicle (2.6% dimethyl sulfoxide [DMSO]) or 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (0.05 microg/microl), an inhibitor of soluble guanylyl cyclase (sGC). ODQ did not affect basal levels of plasma VP or OT; (1b) Rats dehydrated for 24 h received aCSF or 8-Br-cGMP (icv), a membrane-permeable analog of cGMP, and plasma hormones were measured 2 min later. 8-Br-cGMP did not significantly change VP or OT levels; (2) Rats ingested water or 2% NaCl for 4 days, and NO synthase (NOS) and sGC activities were measured in posterior pituitaries, the anatomical site of hormone secretion. Salt loading enhanced (P < 0.001) production of [(14)C]citrulline, the coproduct of NO synthesis, without altering cGMP; (3) One SON was microdialyzed with [(14)C]arginine and NOS and sGC activities were quantified in microdialysates during intravenous (iv) infusion of isotonic or hypertonic saline in awake and anesthetized rats. In awake rats, [(14)C]citrulline recovery, but not cGMP, increased (P < 0.05) during intravenous infusion of both isotonic and hypertonic solutions, and after insertion of microdialysis probe itself. In anesthetized rats, however, where basal NOS activity is low, intravenous infusion of hypertonic, but not isotonic solution, increased [(14)C]citrulline recovery without affecting cGMP. Thus, in the forebrain, neither NO produced basally nor during osmotic stimulation depends on cGMP to modulate plasma vasopressin and oxytocin secretion.
环磷酸鸟苷（cGMP）信号转导机制介导一氧化氮（NO）对下丘脑 - 神经垂体系统中催产素（OT）和血管加压素（VP）分泌的调节作用。在成年雄性斯普拉格 - 道利大鼠中进行了三项研究：（1a）给水分正常的大鼠脑室内（icv）输注（1微升/分钟，持续30分钟）人工脑脊液（aCSF）、溶剂（2.6%二甲亚砜 [DMSO]）或1H - [1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮（ODQ）（0.05微克/微升），后者是可溶性鸟苷酸环化酶（sGC）的抑制剂。ODQ不影响血浆VP或OT的基础水平；（1b）脱水24小时的大鼠接受aCSF或8 - 溴 - cGMP（icv）（cGMP的一种膜通透性类似物），2分钟后测量血浆激素水平。8 - 溴 - cGMP未显著改变VP或OT水平；（2）大鼠饮用4天的水或2%氯化钠溶液，然后测量垂体后叶（激素分泌的解剖部位）中一氧化氮合酶（NOS）和sGC的活性。盐负荷增加了（P < 0.001）[14C]瓜氨酸（NO合成的副产物）的生成量，但未改变cGMP；（3）在清醒和麻醉的大鼠静脉输注等渗或高渗盐水期间，用[14C]精氨酸对一个视上核进行微透析，并对微透析液中的NOS和sGC活性进行定量。在清醒大鼠中，静脉输注等渗和高渗溶液期间以及插入微透析探针后，[14C]瓜氨酸的回收率增加（P < 0.05），但cGMP未增加。然而，在麻醉大鼠中，基础NOS活性较低，静脉输注高渗而非等渗溶液可增加[14C]瓜氨酸的回收率，且不影响cGMP。因此，在前脑，基础状态下或渗透刺激期间产生的NO均不依赖cGMP来调节血浆血管加压素和催产素的分泌。
