顶核—延髓头端腹外侧区系统参与前庭降压降心率反应

实验用乌拉坦麻醉、箭毒化、人工呼吸的大鼠。将神经元胞体兴奋剂L-谷氨酸钠(Glu)微量注入顶核或前庭上核均引起血压下降;心率减慢。该顶核-和前庭上核-降压降心率反应均可被延髓头端腹外侧区内注射GABA受体阻断剂荷包牡丹碱阻断。顶核内注射普鲁卡因也能阻断Glu兴奋前庭上核的心血管反应。以上结果提示前庭-降压降心率反应可能通过顶核-延髓头端腹外侧区系统实现。静脉注射甲基阿托品也能衰减Glu兴奋顶核的心血管反应,显示迷走神经也参与前庭-顶核降压降心率反应。     

延髓腹外侧头端区注射肾上腺髓质素对大鼠血压、心率和肾交感神经活动的影响

本研究在 3 4只麻醉Sprague Dawley大鼠观察了延髓腹外侧头端区内微量注射肾上腺髓质素 ( 10μmol/L ,2 0 0nl)对平均动脉压 (MAP)、心率 (HR)和肾交感神经放电 (RSNA)的影响。实验结果如下 :( 1)延髓腹外侧头端区内微量注射肾上腺髓质素可引起MAP、HR、和RSNA明显增加 ,分别由 99 0 9± 3 3 2mmHg ,3 70 78± 7 84bpm和 10 0± 0 %增至 113 5 7± 3 64mmHg (P <0 0 0 1) ,3 83 2 8± 7 3 8bpm (P <0 0 0 1)和 12 3 72±2 74% (P <0 0 0 1) ;( 2 )降钙素基因相关肽受体阻断剂CGRP8 3 7( 10 0 μmol/L ,2 0 0nl)不能阻断肾上腺髓质素的上述效应 ;( 3 )静脉注射NO前体L 精氨酸 ( 10 0mg/kg ,0 2ml)可消除肾上腺髓质素的上述效应。以上结果提示 ,肾上腺髓质素作用于延髓腹外侧头端区可产生显著的心血管作用 ,此作用不是由降钙素基因相关肽受体介导 ,但可被NO所阻断     

头端延髓腹外侧区在侧脑室注射新斯的明所致升压中的作用

实验在47只乌拉坦(700m/kg)、氯醛糖(35mg/kg)麻醉,肌肉麻痹,人工呼吸的家兔上进行。结果观察到,侧脑室注射(icv)新斯的明引起血压升高,心率(HR)先减慢后有加快趋势,股动脉血流量(FBF)与股动脉血管通道性(COND)减小,左心室内压(LVP)增大,肾交感神经放电(RND)增加,延髓腹外侧头端(rVLM)微量注射阿托品则引起血压下降,HR减慢,FBF与COND增加,LVP与RND减小,若在icv新斯的明之前,预先向rVLM注入阿托品,可阻断新斯的明的升压效应,上述结果提示,rVLM是icv新斯的明升压效应的重要部位,rVLM区M受体功能完整是这种升压作用的关键因素。     

侧脑室注射白细胞介素-2的心血管效应

目的:探讨IL-2的中枢心血管效应及作用机制.方法:SD大鼠脲脂(1.2 g/kg)腹腔麻醉,侧脑室微量注射不同浓度白细胞介素-2(IL-2),及纳络酮、阿托品、酚妥拉明预处理后注射IL-2,观察平均动脉压(MAP)和心率(HR)的改变.结果:侧脑室微量注射IL-2 500 IU和1000 IU对血压与心率无明显影响.注射IL-2 1500 IU,MAP在给药后5min开始升高,10 min达到最高,增幅达(10±1.8)mmHg(P＜0.01),此效应持续15 min,给药25min后恢复至给药前水平;在给药后10 min,心率升高达峰值,增幅达(25±2)b/min(P＜0.05),效应持续10 min;分别用纳络酮、阿托品预处理5 min后,均能阻断IL-2的升压和增加心率的作用.酚妥拉明预处理后,不能阻断IL-2的升压及增加心率的作用.结论:侧脑室注射IL-2可引起大鼠血压增高和心率加快.脑内的阿片系统和胆碱能系统可能参与IL-2的中枢心血管效应.α-肾上腺能受体可能不参与此作用.     

侧脑室注射肾上腺髓质素对大鼠脑内心血管相关核团儿茶酚胺神经元及c-fos表达的影响

目的和方法:利用Fos蛋白和酪氨酸羟化酶(TH)的双重免疫组化方法,观察侧脑室注射肾上腺髓质素对大鼠心血管相关核团中儿茶酚胺神经元及c fos表达的影响,以探讨肾上腺髓质素的中枢效应是否通过激活脑内儿茶酚胺能神经元而诱发。结果:①侧脑室注射肾上腺髓质素(3nmol/kg)诱发脑干、下丘脑及前脑等多个部位的心血管中枢出现大量Fos样免疫反应神经元。②侧脑室注射肾上腺髓质素引起最后区(AP)、孤束核(NTS)、巨细胞旁外侧核(PGL)和蓝斑核(LC)内Fos TH双标神经元明显增加。③降钙素基因相关肽受体拮抗剂CGRP8-37(30nmol/kg)可明显减弱肾上腺髓质素的效应。结论:肾上腺髓质素可兴奋脑干、下丘脑及前脑等多个部位心血管相关核团的神经元,其中枢效应通过激活儿茶酚胺能神经元而诱发,降钙素基因相关肽受体介导这一效应。     

家兔延髓腹外侧区内注射荷包牡丹碱对安定降低心脏功能的影响

家兔48只,用乌拉坦(1g/kg)静脉麻醉,三碘季铵酚制动,在人工呼吸下进行实验。静脉注射安定(0.5mg/kg)以及侧脑室注射氟安定(2mg溶于50μl人工脑脊液中)或γ-氨基丁酸(GABA)(300μg溶于50μl人工脑脊液中)都可降低心室内压峰值(PLVP),减少心力环面积(ACFL)和心室内压最大上升速率(dp/dt_(max))。安定和氟安定对PLVP、ACFL和dp/dt_(max)的抑制作用可被预先在侧脑室注射GABA受体拮抗剂印防己毒素(15μg溶于50μl人工脑脊液中)或双侧延髓腹外侧头端区(γVLM)微量注射GABA受体拮抗剂荷包牡丹碱(3μg溶于0.5μl生理盐水)所阻断。而在延髓网状巨细胞核中间部、网状小细胞核、孤束核或面神经核内注射同样剂量的荷包牡丹碱则不能阻断。 这些结果提示:延髓腹侧部GABA受体的激活可抑制心脏功能,安定对心脏功能的抑制作用可能通过激活延髓腹侧区GABA受体而实现。     

辣椒素对大鼠延髓腹外侧头端区神经元电活动的影响

在35只切断两侧缓冲神经的麻醉大鼠,应用细胞外记录的电生理学方法,观察颈总动脉注射辣椒素(capsaicin)对延髓腹外侧头端区(RVLM)巨细胞旁外侧核(PGL)自发电活动的影响。所得结果如下:(1)颈动脉注射辣椒素(10μmol,01ml),MAP由1074±013升至1256±021kPa(P<0001);HR由374±4增至395±5bpm(P<0001);30个PGL神经元自发放电单位的放电频率由126±07增至209±11spikes/s(P<0001)。(2)在10个放电单位,应用辣椒素受体阻断剂钌红(rutheniumred;200mmol,01ml)后,明显抑制辣椒素的上述效应。以上结果提示,辣椒素可能通过激活RVLM神经元上的辣椒素受体,进而兴奋PGL神经元     

Orexin在隔核对大鼠胃传入信息的调控

目的:研究orexin在隔核对大鼠胃传入信息的调控作用。方法:选取健康成年雄性Wistar大鼠138只(体质量250-300 g),记录神经元放电活动,鉴定隔核胃牵张(GD)敏感性神经元;隔核微量注射orexin-A或orexin-A受体拮抗剂SB334867,观察隔核GD敏感性神经元放电活动变化;隔核微量注射不同浓度的orexin-A,观察大鼠胃运动的变化。结果:隔核微量注射orexin-A的大鼠胃运动幅度和频率显著增加,并呈剂量依赖关系(P0.05-0.01),微量注射SB-334867可完全阻断orexin-A对胃运动的影响。隔核微量注射orexin-A后,有36个GD-E神经元兴奋(P0.01),16个GD-I神经元抑制。Orexin-A受体拮抗剂SB334867可完全阻断orexin-A对GD敏感神经元的作用。结论:隔核注射orexin能促进大鼠胃运动,并影响胃牵张敏感神经元的放电活动。     

延髓腹外侧区微量注射L－NNA和SNP对大鼠血压、心率和肾交感神经活动的影响

在麻醉大鼠观察了向延髓腹外侧区微量注射ＮＯ合成酶抑制剂Ｎ－硝基左旋精氨酸（ＬＮＮＡ）和硝普钢（ＳＮＰ）对血压、心率和肾交感神经活动的影响,旨在探讨中枢左旋精氨酸－ＮＯ通路在动脉血压调节中的作用及其机制。实验结果如下：（１）向延髓腹外侧头端区（ＲＶＬＭ）注射Ｌ－ＮＮＡ后,平均动脉压（ＭＡＰ）升高,肾交感神经活动（ＲＳＮＡ）增强;心率（ＨＲ）减慢,但无统计学意义。ＭＡＰ和ＲＳＮＡ的变化持续３０ｍｉｎ以上;此效应可被预先静注左旋精氨酸所逆转。（２）向ＲＶＬＭ微量注射ＳＮＰ,ＭＡＰ降低,ＲＳＮＡ减弱;但ＨＲ的变化无统计学意义。（３）向延髓腹外侧尾端区（ＣＶＬＭ）注射Ｌ－ＮＮＡ,ＭＡＰ降低,ＨＲ减慢,ＲＳＮＡ减弱。（４）向ＣＶＬＭ微量注射ＳＮＰ,ＭＡＰ升高,ＲＳＮＡ增强,而心率无明显变化。以上结果表明,中枢左旋精氨酸－ＮＯ通路对延髓腹外侧部的神经元活动有调变作用。     

大鼠蓝斑内注入谷氨酸钠的心血管效应及其中枢机制

本工作在乌拉坦麻醉、箭毒化、人工呼吸的大鼠观察到:(1)将 L-谷氨酸钠(Glu)微量注入蓝斑(LC)引起血压升高,心率无明显变化;注入 LC 邻近区引起血压降低、心率减慢。(2)在下丘脑的室旁核尾侧断脑可衰减 LC 加压效应,而室旁核头侧断脑对 LC 加压反应无明显影响,双侧延髓头端腹外侧区(RVL)内分别注射酚妥拉明、心得安、阿托品均使兴奋 LC 引起的加压效应衰减;提示蓝斑加压效应由室旁核和 RVL(及其内的α-、β-肾上腺素能受体,M-胆碱能受体)介导。     

Medullary pathways mediating the parasubthalamic nucleus depressor response

The parasubthalamic nucleus (PSTN) projects extensively to the nucleus of the solitary tract (NTS); however, the function of PSTN in cardiovascular regulation is unknown. Experiments were done in alpha-chloralose anesthetized, paralyzed, and artificially ventilated rats to investigate the effect of glutamate (10 nl, 0.25 M) activation of PSTN neurons on mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Glutamate stimulation of PSTN elicited depressor (-20.4 +/- 0.7 mmHg) and bradycardia (-26.0 +/- 1.0 beats/min) responses and decreases in RSNA (67 +/- 17%). Administration (intravenous) of atropine methyl bromide attenuated the bradycardia response (46%), but had no effect on the MAP response. Subsequent intravenous administration of hexamethonium bromide blocked both the remaining bradycardia and depressor responses. Bilateral microinjection of the synaptic blocker CoCl(2) into the caudal NTS region attenuated the PSTN depressor and bradycardia responses by 92% and 94%, respectively. Additionally, prior glutamate activation of neurons in the ipsilateral NTS did not alter the magnitude of the MAP response to stimulation of PSTN, but potentiated HR response by 35%. Finally, PSTN stimulation increased the magnitude of the reflex bradycardia to activation of arterial baroreceptors. These data indicate that activation of neurons in the PSTN elicits a decrease in MAP due to sympathoinhibition and a cardiac slowing that involves both vagal excitation and sympathoinhibition. In addition, these data suggest that the PSTN depressor effects on circulation are mediated in part through activation of NTS neurons involved in baroreflex function.     

Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract

Experiments were done in male Wistar rats to investigate the effects of microinjection of hypocretin-1 (Hcrt-1) into the nucleus of the solitary tract (NTS) on mean arterial pressure (MAP), heart rate (HR), and the baroreflex. In the first series, the distribution of Hcrt-1-like immunoreactivity (Ir) was mapped within the region of NTS. Hcrt-1 Ir was found throughout the NTS region, predominantly within the caudal dorsolateral (Slt), medial (Sm), and interstitial subnuclei of the NTS. In the second series, in alpha-chloralose or urethane-anesthetized rats, microinjection of Hcrt-1 (0.5-5 pmol) into the caudal NTS elicited a dose-dependent decrease in MAP and HR. A mapping of the caudal NTS region showed that the largest depressor and bradycardia responses elicited by Hcrt-1 were from sites in the Slt and Sm. In addition, doses >2.5 pmol at a small number of sites localized to the caudal commissural nucleus of NTS elicited pressor and tachycardia responses. Intravenous administration of the muscarinic receptor blocker atropine methyl bromide abolished the bradycardia response and attenuated the depressor response, whereas subsequent administration of the nicotinic receptor blocker hexamethonium bromide abolished the remaining MAP response. Finally, microinjection of Hcrt-1 into the NTS significantly potentiated the reflex bradycardia to activation of arterial baroreceptors as a result of increasing MAP by systemic injections of phenylephrine (2-4 microg/kg). These results suggest that Hcrt-1 in the NTS activates neuronal circuits that increases vagal activity to the heart, inhibits sympathetic activity to the heart and vasculature, and alters the excitability of NTS neuronal circuits that reflexly control the circulation.     

侧脑室注射硫化氢对大鼠血压和呼吸的调节作用

目的 探讨中枢硫化氢（H2S）对正常大鼠平均动脉血压的调节及其机制.方法 将微量H2S饱和盐溶液一次性和连续注射入麻醉大鼠侧脑室（ICV）,观察注药后血压、心率和呼吸的变化.结果 ICV一次性注射不同剂量的H2S饱和盐溶液后可引起血压先急剧降低而后迅速升高,心率减慢,呼吸幅度增加和呼吸频率减慢,并存在显著的剂量和时间依赖关系.ICV连续注射H2S可显著升高血压,但对心率和呼吸没有影响.ICV注射一次性注射K＋-ATP通道开放剂Pinacidil可显著的降低血压,但心率和呼吸没有显著变化;ICV一次性注射K＋-ATP通道阻断剂glibenclamide对血压、心率和呼吸没有显著的影响;但预先ICV注射glibenclamide可阻断H2S的降低血压和减慢心率的作用,对呼吸没有影响.预先静脉注射酚妥拉明对血压没有明显的影响,却显著抑制ICV给予H2S产生的升高血压减慢心率效应.结论 本工作提示H2S是调节心血管活动的一个重要的中枢活性因子,其降低血压的效应是通过K＋-ATP通道和影响呼吸有关系,而升压效应是通过激活交感神经的活性.     

最后区注射腺苷对大鼠血压、心率和肾交感神经放电的影响

在 5 3只麻醉Sprague Dawley大鼠观察了最后区内微量注射腺苷 (1ng/ 6 0nl)对平均动脉压 (MAP)、心率(HR)和肾交感神经放电 (RSNA)的影响。实验结果如下 :(1)最后区内微量注射Ado后 ,MAP、HR和RSNA分别由13 76± 0 46kPa、35 6 2 8± 4 2 5bpm和 10 0± 0 %下降至 11 2 3± 0 49kPa (P <0 0 0 1)、336 91± 5 2 3bpm (P <0 0 1)和70 95± 5 19% (P <0 0 0 1) ;(2 )静脉注射非选择性腺苷受体拮抗剂 8 苯茶碱 (8 phenyltheophylline,15 0 μg/kg ,0 2ml)和选择性腺苷A1受体拮抗剂 (8 cyclopentyl 1,3 dipropylxanthine,5 0 0 μg /kg ,0 2ml)后 ,腺苷的上述抑制效应可被完全阻断 ;(3)静脉注射ATP敏感性钾通道阻断剂格列苯脲 (5mg/kg ,0 2ml)后 ,腺苷的上述效应也被消除。以上结果提示 ,最后区微量注射腺苷对血压、心率和肾交感神经放电有抑制作用 ,此作用与A1受体介导的ATP敏感性钾通道开放有关。     

最后区注射腺苷对大鼠血压,心率和肾交感神经放电影响

The effects of microinjection of adenosine (Ado) into area postrema (AP) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were examined in 53 anesthetized Sprague Dawley rats. The results obtained are as follows. (1) Following microinjection of Ado (1 ng/60 nl) into AP, MAP, HR and RSNA were decreased from 13.76+/-0.46 kPa, 356.28+/-4.25 bpm and 100+/-0% to 11.23+/-0.49 kPa (P<0.001), 336.91+/-5.23 bpm (P<0.01) and 70.95+/-5.19% (P<0.001), respectively; (2) 8-phenyltheophylline (150 microgram/kg, 0.2 ml,iv), a nonselective adenosine receptor antagonist, and 8-cyclopentyl-1,3-dipropylxanthine (500 microgram/kg, 0.2 ml, iv), a selective A(1) adenosine receptor antagonist, blocked the inhibitory effect of Ado completely; and (3) glibenclamide (5 mg/kg, 0.2 ml, iv), a blocker of ATP-sensitive potassium channel, also abolished the effect of Ado. The above results indicate that microinjection of Ado into AP induces inhibitory effects on MAP, HR and RSNA, which may be related to activation of ATP-sensitive potassium channels mediated by A(1) receptors.     

Mechanisms involved in the cardiovascular alterations immediately after spinal cord injury

The early cardiovascular effects resulting from an acute spinal cord injury (SCI) produced by a contusion procedure at T5-T6 were evaluated in anaesthetized rats. The mean arterial pressure (MAP) and heart rate (HR) were measured during one hour after the injury. A marked decrease in MAP and HR was observed immediately after injury, followed by an abrupt increase in MAP. These changes were observed between 3 and 9 min and the basal values were recovered after 20 min. Fall in the MAP and HR and increase in MAP induced by SCI were abolished by atropine. The interruption of the parasympathetic outflow by vagotomy also significantly diminished the fall and increase in MAP and the fall in HR. Likewise, pre-treatment with nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) completely abolished the effects produced by SCI. These data suggest that after SCI the decrement in MAP and HR was probably due to acetylcholine release from parasympathetic fibers and NO from endothelial source probably by a cholinergic stimulation. Additionally, the MAP increase observed was probably due to a reflex compensatory vasoconstriction.     

The effects of acute and chronic alpha melanocyte stimulating hormone (alphaMSH) on cardiovascular dynamics in conscious rats

Alpha melanocyte stimulating hormone (alphaMSH) has been demonstrated to have regulatory functions in the periphery and central nervous system (CNS). alphaMSH plays a central role in the regulation of metabolic balance such as decreasing food intake, increasing sympathetic outflow and hypothalamic/pituitary function. Our laboratory has investigated the actions of alphaMSH on sympathetic and cardiovascular dynamics using anesthetized animals. In this study we determined both the acute and chronic effects of alphaMSH on cardiovascular and metabolic dynamics in conscious unrestrained rats. Animals were each implanted with a radio-telemetry transmitter for recording of cardiovascular parameters and subsequently instrumented with intracerebroventricular (ICV) cannulas. The acute ICV administration of alphaMSH significantly increased the mean arterial pressure (MAP) and heart rate (HR) when compared to artificial cerebrospinal fluid (ACSF) controls. On the other hand chronic alphaMSH infusion resulted in an initial increase in MAP and HR lasting for 2 days followed by a decrease in MAP. Chronic alphaMSH administration decreased physical activity and food intake but not weight gain. We conclude that in the conscious unrestrained animal the acute administration of alphaMSH increased MAP and HR, however, chronic infusion is associated with decreased MAP, physical activity and food intake.     

Cardiac effects of hypocretin-1 in nucleus ambiguus

Although recent studies have reported hypocretin 1 (hcrt-1)-like-immunoreactivity (ir) within the region of the nucleus ambiguus (Amb) in the caudal brain stem, the function of hcrt-1 in the Amb on cardiovascular function is not known. Three series of experiments were done in male Wistar rats to investigate the effects of microinjections of hcrt-1 into Amb on heart rate (HR), mean arterial pressure (MAP), and the arterial baroreceptor reflex. In the first series, a detailed mapping of the distribution of hcrt-1- and hcrt-1 receptor (hcrtR-1)-like-ir was obtained of the Amb region. Although hcrt-1-like- and hcrtR-1-like-ir were found throughout the rostrocaudal extent of the Amb and adjacent ventrolateral medullary reticular formation, most of the hcrtR-1-like-ir was observed in the area just ventral to the compact formation of Amb, in the region of the external formation of the nucleus (Ambe). In the second series, the Amb region that contained hcrt-1 and hcrtR-1-ir was explored for sites that elicited changes in HR and MAP in urethane and alpha-chloralose-anesthetized rats. Microinjections of hcrt-1 (0.5-2.5 pmol) into the Ambe elicited a dose-related decrease in HR, with little or no direct change in MAP. The small decreases in MAP were found to be secondary to the HR changes. The largest bradycardia responses were elicited from sites in the Ambe. Administration (iv) of the muscarinic receptor antagonist atropine methyl bromide or ipsilateral vagotomy abolished the HR response, indicating that the HR response was due to activation of vagal cardiomotor neurons. In the final series, microinjections of hcrt-1 into the Ambe significantly potentiated the reflex bradycardia elicited by activation of the baroreflex as a result of the increased MAP after the intravenous injection of phenylephrine. These data suggest that hcrt-1 in the Ambe activates neuronal systems that alter the excitability of central circuits that reflexly control the circulation through the activation of vagal preganglionic cardioinhibitory neurons.     

蓝斑区去甲肾上腺素能神经元在Orexin促麻醉觉醒中的作用研究

目的：探讨蓝斑区（LC）去甲肾上腺素能神经元在orexin促麻醉觉醒中作用。方法：应用异氟烷对成年SD大鼠进行麻醉,15分钟后,将SD大鼠随机分为6组,分别注射orexin-A/B（100pmol/0.3μL）及其溶剂saline（0.3μL）;orexin I型受体拮抗剂SB334867/II型受体拮抗剂TCS-OX2-29（20μg/0.3μL及其溶剂DMSO（0.3μL）,通过观察大鼠翻正反射的消失和恢复时间,研究蓝斑区微注射orexin及其拮抗剂对异氟烷麻醉的诱导和觉醒的影响。结果：蓝斑区（LC）微注射四种试剂或其溶剂均对SD大鼠异氟烷麻醉的诱导时间无明显影响;蓝斑区（LC）微注射orexin-A能缩短SD大鼠异氟烷麻醉觉醒时间（P〈0.001）,而微注射orexinI型拮抗剂SB334867能延长觉醒时间（P〈0.001）;orexin-B、orexin II型受体拮抗剂TCS-OX2-29对大鼠异氟烷麻醉的觉醒无明显影响。结论：蓝斑区（LC）的去甲肾上腺素能神经元介导了orexin的促麻醉觉醒作用。