title: A study on the mechanism by which sodium nitroprusside, a nitric oxide donor, applied to the anteroventral third ventricular region provokes facilitation of vasopressin secretion in conscious rats.
abstract: 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.
authors.affiliation: Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. kenbo@med.niigata-u.ac.jp
authors.forename: Ken'ichi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hama
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002712:Chlorides / Q000097:blood; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D008751:Methylene Blue / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D020542:Third Ventricle / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014667:Vasopressins / Q000097:blood / Q000378:metabolism*
chemical_list: D002712:Chlorides; D006454:Hemoglobins; D020030:Nitric Oxide Donors; D014667:Vasopressins; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D012964:Sodium; D006152:Cyclic GMP; D011188:Potassium; D008751:Methylene Blue