Yamaguchi Ken'ichi, Hama Hitoshi
Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan.
Brain Res. 2003 Apr 4;968(1):35-43. doi: 10.1016/s0006-8993(02)04246-4.
We reported previously that sodium nitroprusside (SNP) applied to the anteroventral third ventricular region (AV3V), a pivotal area for autonomic functions, facilitates vasopressin (AVP) secretion in conscious rats. The aim of this study was to pursue the problems of whether nitric oxide (NO) generated from the agent may be responsible for the phenomenon, and whether it may be mediated by cyclic guanosine monophosphate (cGMP), the biosynthesis of which could reportedly be activated by NO. The infusion of SNP into the AV3V of conscious rats produced dose-related increases in plasma AVP, the maximal responses of which appeared at 5 min. Blood pressure and heart rate tended to rise at 15 min. The plasma osmolality, sodium, potassium or chloride did not show marked alteration following the SNP administration. Although the SNP solution was hypertonic and hypernatremic, AV3V application of hypertonic saline with a relatively higher osmolality and an equal sodium level was significantly less effective in augmenting plasma AVP. When injected into the lateral ventricle, SNP did not change plasma AVP and reduced arterial pressure, different from the results provoked by the AV3V application. The rise in plasma AVP in response to the AV3V application of SNP was diminished by preadministration of hemoglobin, a scavenger of NO, that did not affect the responses of the other variables. In contrast, pretreatment with methylene blue, an agent capable of antagonizing the potency of NO to activate guanylate cyclase, did not attenuate but potentiated the responses of both plasma AVP and arterial pressure to the AV3V infusion of SNP. Hemoglobin or methylene blue given alone into the AV3V did not affect any of the variables monitored. On the other hand, the AV3V injection of 8-bromo cGMP, a stable analogue of cGMP, was not potent for causing a significant rise in plasma AVP, in contrast to the notable AVP-enhancing effect of 8-bromo cAMP. Arterial pressure and heart rate were elevated by both of these agents, whereas the remaining variables were not altered. Histological inspection indicated that the infusion sites of the drugs in the AV3V had included areas such as the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial preoptic nucleus and periventricular nucleus. On the basis of these results, we concluded that the AVP secretion prompted by the AV3V application of SNP may be attributable to NO, whereas its well-known ability to stimulate guanylate cyclase activity may hardly contribute to this phenomenon.
我们之前报道过，将硝普钠（SNP）应用于自主神经功能的关键区域——腹前第三脑室区域（AV3V），可促进清醒大鼠的血管加压素（AVP）分泌。本研究的目的是探讨该药物产生的一氧化氮（NO）是否可能是导致这一现象的原因，以及它是否可能由环磷酸鸟苷（cGMP）介导，据报道cGMP的生物合成可被NO激活。向清醒大鼠的AV3V输注SNP可使血浆AVP呈剂量相关增加，最大反应出现在5分钟时。血压和心率在15分钟时趋于升高。给予SNP后，血浆渗透压、钠、钾或氯未显示出明显变化。尽管SNP溶液为高渗和高钠溶液，但应用渗透压相对较高且钠水平相同的高渗盐水对增强血浆AVP的效果明显较差。当注入侧脑室时，SNP不会改变血浆AVP但会降低动脉压，这与AV3V给药所引发的结果不同。预先给予血红蛋白（一种NO清除剂）可减弱因AV3V应用SNP引起的血浆AVP升高，而血红蛋白对其他变量的反应没有影响。相反，用亚甲蓝预处理（一种能够拮抗NO激活鸟苷酸环化酶能力的药物）并没有减弱反而增强了血浆AVP和动脉压对AV3V输注SNP的反应。单独将血红蛋白或亚甲蓝注入AV3V对所监测的任何变量均无影响。另一方面，与8-溴环磷酸腺苷（8-bromo cAMP）显著的AVP增强作用相反，向AV3V注射8-溴环磷酸鸟苷（8-bromo cGMP，cGMP的一种稳定类似物）对引起血浆AVP显著升高的作用不强。这两种药物均可使动脉压和心率升高，而其余变量未改变。组织学检查表明，药物在AV3V的输注部位包括终板血管器、视前正中核、视前内侧核和室旁核等区域。基于这些结果，我们得出结论，AV3V应用SNP促使AVP分泌可能归因于NO，而其众所周知的刺激鸟苷酸环化酶活性的能力可能对这一现象几乎没有作用。
