隔区和第Ⅲ脑室注射精氨酸加压素对家兔视前区—下丘脑前…

为了研究精氨酸加压素（ＡＶＰ）的抗热机理,本研究观察了家兔隔区和第Ⅲ脑室微量注射ＡＶＰ对视前区－下丘脑前部（ＰＯ－ＡＨ）温度敏感神经元放电的影响。结果如下：（１）隔区注射ＡＶＰ能使ＰＯ－ＡＨ热敏神经元放电明显增加,冷敏神经元放电明显减少。（２）第Ⅲ脑室注射ＡＶＰ只能使部分ＰＯ－ＡＨ热敏神经元放电增加,冷敏神经元放电减少;而另外一部分热敏神经元和冷敏神经元则出现相反的效应。实验结果表明,隔区注射ＡＶ     

隔区注射AVP和AVP抗血清对家兔温敏神经元放电的影响

精氨酸加压素可能是一种内源性退热剂,其抗热作用的最敏感点位于大脑边缘系统的隔区。为了研究ＡＶＰ抗热的作用的机理,本文观察了隔区注射ＡＶＰ和ＡＶＰ抗血清对家兔视前区－下丘脑前部温度敏感神经元放电活动的影响。实验结果如下：１（１）隔区注射ＡＶＰ能使ＰＯ－ＡＨ热敏神经元放电明显增加,冷敏神经元放电明显减少;而隔区注＝谢人工脑脊液对热敏神经元和冷敏神经元的放电均无明显影响。（２）隔区注射ＡＶＰ抗血清后,Ｐ     

杏仁内侧核注射AVP和AVPMcAb对家兔ET性发热效应的影响

目的和方法：在大脑杏仁内侧核微量注射精氨酸加压素（ＡＶＰ）和精氨酸加压素单克隆抗体（ＡＶＰＭｃＡｂ）,观察其对家兔内毒素（ＥＴ）性发热效应以及视前区一下丘脑前部（ＰＯＡＨ）温敏神经元放电活动的影响。结果：①杏仁内侧核微量注射ＡＶＰ能明显抑制家兔ＥＴ性发热效应,注射ＡＶＰＭｃＡｂ能明显易化家兔ＥＴ性发热效应;②杏仁外侧核分别注射ＡＶＰ和ＡＶＰＭｃＡｂ则对家兔ＥＴ性发热效应无明显影响;③杏仁内侧核分别注射ＡＶＰ和ＡＶＰＭｃＡｂ后ＰＯＡＨ热敏神经元和冷敏神经元放电活动均无明显变化。结论：家兔杏仁内侧核也是ＡＶＰ抗热效应的一个重要的作用部位,杏仁内侧核注射ＡＶＰ的抗热作用途径与隔区注射ＡＶＰ的抗热途径可能不同     

葛根素,生石膏配伍对致热原作用下猫POAH温敏神经元放电…

应用微电极细胞外记录技术,在３４只猫ＰＯＡＨ区记录了温敏神经元单位放电,研究中药葛根素和生石膏解热可能的中机制。致热原使４例热敏神经元放电频率减少;使１１例冷敏神经元放电频率增加,注射等量葛根素和生石膏能反转上述作用。致热原及二药对５例温度不敏感神经元放电无影响。结果显示,葛根素和生石膏是影响致热原作用下ＰＯＡＨ区温敏神经元的电活动而解热的。二者配伍使用对冷敏神经元放电频率的影响比单独使用作用强,     

葛根素、生石膏配伍对致热原作用下猫POAH温敏神经元放电的影响

应用微电极细胞外记录技术,在３４只猫ＰＯＡＨ区记录了温敏神经元单位放电,研究中药葛根素和生石膏解热可能的中枢机制。致热原使１４例热敏神经元放电频率减少;使１１例冷敏神经元放电频率增加。注射等量葛根素和生石膏能反转上述作用。致热原及二药对５例温度不敏感神经元放电无影响。结果显示,葛根素和生石膏是影响致热原作用下ＰＯＡＨ区温敏神经元的电活动而解热的。二者配伍使用对冷敏神经元放电频率的影响比单独使用作用强,提示在中枢水平二者有协同作用。     

侧脑室注射AVP与微电泳AVP对家兔隔区温敏神经元放电活动的影响

隔区不仅分布大量的精氨酸加压素 (ＡＶＰ)神经元 ,而且也分布温敏神经元 ,参与生理性与行为性体温调节。本文观察了侧脑室注射ＡＶＰ和微电泳ＡＶＰ对隔区温敏神经元放电活动的影响 ,以证明隔区注射ＡＶＰ的抗热作用是否与ＡＶＰ直接影响 ,隔区温度敏感神经元的活动有关。1　材料与方法选用体重 1 8～ 2 6ｋｇ家兔 36只 ,用 2 5 %乌拉坦溶液静脉麻醉 (1 ｇ/ｋｇ) ,完成有关手术。用直流恒温电热毯裹住家兔躯体 ,使肛温维持在 38 5℃。隔区温敏神经元放电活动的记录定位按Ｓａｗｙｅｒ兔脑图谱取Ａ3～ 5,Ｌ1～ 2 5,Ｈ5～ 9(脑表面下 …     

丁香酚对大鼠弓状核温度敏感神经元电活动的影响

本实验采用微电极细胞外记录技术,在大鼠弓状核记录到单一放电单位６８例,其中热敏神经元１１例,占１６．２％,冷敏神经元２５例,占３６．８％;温度不敏感神经元３２例,占５３％。本实验同时观察了皮下注射丁香酚（２０μｇ／１００ｇ）对温度敏感神经元放电活动的影响,其结果为１０例冷敏神经元的放电频率均减慢;４例热敏神经元的放电频率均增快;而１４例温度不敏感神经元的放电活动则无明显改变。以上结果表明弓状核内存在以冷敏神经元居多的温度敏感神经元,并探讨了丁香酚的降温作用与它能够抑制弓状核的冷敏神经元,激活热敏神经元的电活动有关,亦成为弓状核参与体温调节的有力佐证     

中枢注射U－50，488H对肾水钠钾的排出及PVH内TH－IR神经元活性的影啊

本工作用１２％乙醇麻醉的大鼠,观察了下丘脑室旁核（ＰＶＨ）微量注射Ｋ型阿片受体激动剂Ｕ－５０,４８８Ｈ对大鼠肾水钠钾排出的影响,以及第三脑室注射Ｕ－５０,４８８Ｈ对ＰＶＨ中多巴胺神经元活性的影响。结果如下：（１）ＰＶＨ微量注射Ｕ－５０,４８８Ｈ（５μｎ／ｕｌ）后２０ｍｉｎ内大鼠尿量开始增加（Ｐ＜０．０１）,持续约１００ｍｉｎ,４１—６０ｍｉｎ尿量增加达峰值（Ｐ＜０．００１）。（２）ＰＶＨ预先（１０ｍｉｎ）注射Ｋ型阿片受体阻断剂ＮＢＴ（Ｎｏｒ－ＢｉｎａｌｔｏｒｐｈｉｍｉｎｅＴｅｔｒａｈｙｄｒａｔｅ）（５μｇ／ｐｌ）可以阻断Ｕ－５０,４８８Ｈ所产生的利尿效应（Ｐ＜０．０１）。（３）第三脑室注射Ｕ－５０,４８８Ｈ（１０μｇ／１０ｕｌ）２０ｍｉｎ后,ＰＶＨ中酪氨酸羟化酶免疫反应阳性（Ｔｙｒｏｓｉｎｅｈｙｄｒｏｘｙｌａｓｅ－ｉｍｍｕｎｏｒｅａｃｔｉｖｉｔｙ,ＴＨ－ＩＲ）神经元数量减少,染色强度减弱,于注药后５０ｍｉｎ变化最为显著,１００ｍｉｎ时已恢复正常。上述结果表明：ＰＶＨ微量注射Ｕ－５０,４８８Ｈ可作用于Ｋ型阿片受体引起利尿效应;第三脑室微量注射Ｕ－５０,４８８Ｈ可抑制ＰＶＨ中ＴＨ－ＩＲ神经元的免疫活性。     

L－NNA及NO供体对延髓腹外侧头端区神经元自发放电的影响

在麻醉大鼠观察了静注ＮＯ合成酶抑制剂Ｎ－硝基左旋精氨酸（Ｌ－ＮＮＡ）和ＮＯ供体──硝普钠（ＳＮＰ）和ＳＩＮ－Ｉ对血压、心率和延髓腹外侧头端区（ＲＶＬＭ）神经元自发放电活动的影响,旨在探讨Ｌ－ａｒｇ：ＮＯ通路对动脉血压调节的中枢作用部位。所得结果如下：（１）静注Ｌ－ＮＮＡ后,平均动脉压（ＭＡＰ）升高,心率（ＨＲ）加快,１１个ＲＶＬＭ神经元自发放电频率增加。这些变化发生于给药后５ｍｉｎ,持续时间达３０ｍｉｎ以上。（２）静注ＳＮＰ后,ＭＡＰ降低,ＨＲ加快,２３个ＲＶＬＭ神经元自发放电频率降低,且有剂量依赖性。ＳＮＰ作用发生快,持续时间短。为了排除脑缺血的影响,还特意向一侧颈动脉内注射相同剂量ＳＮＰ,结果引起ＭＡＰ轻度降低,而ＨＲ无明显改变,但ＲＶＬＭ神经元自发放电频率仍显著降低。（３）静注另一ＮＯ供体ＳＩＮ－Ｉ后,ＭＡＰ降低,１１个ＲＶＬＭ神经元自发放电频率降低．与ＳＮＰ的效应基本一致。以上结果提示,ＲＶＬＭ是Ｌ－ａｒｇ：ＮＯ通路实现动脉血压调节的一个中枢作用部位。     

中枢注射U—50,488H对肾水钠钾的排出及PVH内TH —IR神经元活性的影响

本工作１２％乙醇麻醉的大鼠,观察了下丘脑室旁核（ＰＶＨ）微量注射Ｋ型阿片受体激动剂Ｕ－５０,４８８Ｈ对大鼠肾水钠钾排出的影响,以及第三脑室注射Ｕ－５０,４８８Ｈ对ＰＶＨ中多马上胺神经元活性的影响。结果如下（１）ＰＶＨ微量注射Ｕ－５０,４８８Ｈ（５μｇ／ｌ）后２０ｍｉｎ内大量尿量开始增（Ｐ＜０．０１）,持续约１００ｍｉｎ,,４１－６０ｍｉｎ尿量增加达峰值（Ｐ＜０．００１）。（２）,ＰＶＨ预先（１０ｍ     

家兔发热时脑脊液和血浆中精氨酸加压素含量的变化及禁水的抗热作用

本实验观察了发热家兔脑脊液(CSF)和血浆中精氨酸加压素(AVP)含量的变化及禁水对家兔内毒素(ET)发热效应的影响。实验结果表明:1.隔区注射AVP可明显抑制家兔ET性发热效应;2.发热组家兔CSF和血浆中AVP含量较正常组明显降低;3.禁水可明显对抗家兔ET性发热效应,其抗热作用与CSF和血浆中AVP含量升高有关;4.禁水也可使正常家兔体温水平下移。上述实验结果提示,AVP可能是家兔体内一种内源性退热物质,同时在正常体温调节中也可能发挥一定的作用。     

中枢精氨酸加压素在大鼠促肾上腺皮质激素释放激素释放激素引起发热机制中的作用

实验对大鼠进行第三脑室和脑腹中隔区插管,用数字体温计测量大鼠的结肠温度,用放射免疫分析法测定脑中隔区精氨酸加压素（arginine vasopressin,AVP）含量,观察脑中隔区AVP在大鼠促肾上腺皮质激素释放激素（corticotrophin releasing hormone,CRH）性发热机制中的作用。结果发现：脑室注射CRH（5.0μg）引起大鼠结肠温度明显升高,同时明显增高脑中隔区AVP的含量。脑腹中隔区注射AVP V1受体拮抗剂本身并不导致大鼠结肠温度明显改变,但能显著增强脑室注射CRH引起的发热反应。而且,腹中隔区注射AVP显著抑制大鼠CRH性发热。结果提示：发热时CRH是引起脑腹中隔区AVP释放的因素之一,脑腹中隔区内源性AVP抑制中枢注射CRH引起的体温升高。     

Intracerebroventricular and septal injections of arginine vasopressin are not antipyretic in the rabbit

Arginine vasopressin (AVP) has been reported to have an antipyretic effect in the ewe and guinea pig near term. Perfusions with AVP of sites in the septal region also reduced fever in non-pregnant sheep. In the present experiments adult rabbits with third cerebral ventricular or septal cannulas were restrained in a 23°C environment, and rectal temperature was recorded every 10 min. Fever induced by IV administration of leukocytic pyrogen was not reduced by AVP (25–100 ng) given intraventricularly 20 min later. Doses of 1–5 μg AVP injected into the septum likewise were not antipyretic but actually caused an increase in fever. This augmentation of the febrile response is consistent with results of previous studies in this laboratory in which AVP increased hyperthermia in a hot environment and enhanced hyperthermic responses to PGE₂. The data from these experiments provide no evidence that central AVP is an endogenous antipyretic in rabbits; rather, it may be that central AVP augments fever in this species.     

Iontophoretic mapping of corticotropin-releasing factor (CRF) sensitive neurons in the rat forebrain

Iontophoretic application of corticotropin-releasing factor (CRF) onto the membrane of individual brain neurons produced changes in the spontaneous occurrence of their extracellular action potentials. Neurons in the cortex and hypothalamus tended to be excited by the application of this 41-residue peptide, while those in the thalamus and lateral septal area were inhibited. In general, neurons excited by CRF were also inhibited by the local application of dopamine (DA) and morphine (MOR), while those which were inhibited by CRF were excited by DA and MOR. Glutamate excited the majority of cells tested independent of the other peptide responses. The results suggest that CRF activates several CNS regions with some specificity, and may be involved in neuronal modulation of pituitary as well as extrapituitary events.     

Evidence for antipyretic vasopressinergic pathways and their modulation by noradrenergic afferents.

The experimental evidence for the antipyretic action of arginine vasopressin (AVP) in guinea-pigs can be summarized as follows: The febrile response to a bacterial pyrogen can be reduced by a microinfusions of exogenous AVP into the ventral septal area of the limbic system. Immunohistochemical studies indicate increased activity of AVP terminals in the ventral septal area (VSA) and in parvocellular AVP neurones of the hypothalamic paraventricular nucleus (PVN) in several stressful situations accompanied by reduced febrile responses (late stage of pregnancy, immobilization, cold adaptation, osmotic stimulation). Also the peripheral and/or central release of AVP measured in some of these situations is increased. Electrical stimulation of the PVN suppresses fever, this suppression can, at least partly, be cancelled by simultaneous intraseptal application of the vasopressinergic V1 receptor antagonist. The documented AVP pathways from the PVN to the septum receive noradrenergic afferents from the lower brainstem. Chronic destruction of these afferents by microinjections of 6-hydroxydopamine (6-OHDA) significantly reduced the fever responses to pyrogen application, while microinfusion of noradrenaline (NA) enhances the fever reaction.     

Effects of angiotensin and vasopressin V(1) receptors on water and sodium intake induced by injection of vasopressin into lateral septal area

The specific arginine(8)-vasopressin (AVP) V(1) receptors antagonist (AAVP) was injected (20, 40 and 80 nmol) into the lateral septal area (LSA) to determine the effects of selective septal V(1) receptor on water and 3% sodium intake in rats. Was also observed the effects of losartan and CGP42112A (select ligands of the AT(1) and AT(2) ANG II receptors, respectively) injected into LSA prior AVP on the same appetites. Twenty-four hours before the experiments, the rats were deprived of water. The volume of drug solution injected was 0.5 microl. Water and sodium intake were measured at 0.25, 0.5, 1.0 and 2.0 h. Injection of AVP reduced the water and sodium ingestion vs. control (0.15 M saline). Pre-treatment with AAVP (40, 80 and 160 nmol) did not alter the decrease in the water ingestion induced by AVP, whereas AAVP abolished the action of AVP-induced sodium intake. Losartan (40, 80 and 160 nmol) did not alter the effect of AVP on water and sodium intake, whereas CGP42112A (20, 40 and 60 nmol) at the first 30 min increased water ingestion. Losartan and CGP42112A together increased the actions of AVP, showing more pronounced effects than when the two antagonists were injected alone. The results showed that AVP inhibited the appetites and these effects were increased by the AAVP. The involvement of angiotensinergic receptors in the effects of AVP is also suggested.     

Central vasopressin V1-blockade prevents salicylate but not acetaminophen antipyresis

Recent evidence has suggested that the endogenous antipyretic arginine vasopressin (AVP) may participate in drug-induced antipyresis. This study sought to further those investigations by comparing the effects of two other antipyretic drugs, sodium salicylate and acetaminophen, administered intraperitoneally, during AVP V1-receptor blockade within the ventral septal area (VSA) of the rat brain. During endotoxin-evoked fever, V1-receptor blockade within the VSA of the conscious unrestrained rat significantly antagonized the antipyretic effects of salicylate. The effects of the V1-antagonist on salicylate-induced antipyresis were dose related. In contrast, the antipyresis elicited by acetaminophen was unaffected by VSA V1-antagonist pretreatment. Neither saline nor the V1-antagonist microinjected into the VSA of febrile or nonfebrile rats had any significant effects on the normal progression of endotoxin fever or normal core temperature, respectively. These data suggest that the mechanism of action of salicylate-induced antipyresis includes activation of AVP V1-type receptors within the VSA, as has been shown for indomethacin. However, the lack of effect of the V1-antagonist on antipyresis induced by acetaminophen indicates that not all antipyretic drugs act through the same mechanism in the brain.