刺激家兔腹部迷走神经外周端降压效应中枢机制的研究

应用电解损毁和脑室内注射药物的方法研究了刺激家兔腹部迷走神经外周端所致降压效应的中枢机制。结果表明:1.电刺激延脑闩部尾侧1.5—2mm、中线旁开0.25mm、深1—2mm 处主要引起降压反应。2.电解损毁该部位可以使刺激腹部迷走神经外周端所引起的降压效应显著减弱(n=20,P<0.001),但对刺激减压神经所致降压反应无影响。3.在延脑闩部水平电解损毁减压神经纤维在孤束核的主要投射区可以使刺激减压神经所致降压反应显著减弱,而对刺激腹部迷走神经外周端所致降压反应无影响。4.第四脑室注射5,6-双羟色胺的动物较之注射人工脑脊液的动物颈、胸髓5-羟色胺含量明显降低、动物动脉压增高、心率明显增快、刺激减压神经所致降压反应未见减弱,而刺激腹部迷走神经外周端所致降压反应却明显减小。因此,我们认为家兔腹部迷走神经外周端所致降压效应依赖于延脑闩下部的中缝隐核及连合核等结构,而与减压神经的投射部位无关。延脑中缝核至脊髓的下行性5-HT能神经纤维抑制脊髓交感节前神经元的活动,是这个降压效应的中枢机制之一。     

腹部迷走神經对血压的作用

(一)电刺激猫腹部迷走神经中枢端和外周端与兔腹部迷走神经中枢端均引起快速升压反应,而刺激兔腹部迷走神经外周端则为降压反应。无论刺激其中枢端或外周端在猫均伴有明显的瞳孔扩张,而兔则无此现象。 (二)刺激动物腹部迷走神经引起的升压反应是通过延脑血管舒缩中枢所致的交感性缩血管作用,其中枢端的加压效应主要是由颈迷走神经传入的,猫外周端的加压效应则是由内脏大神经传入。腹部迷走神经与内脏大神经中传入纤维的联系机制尚待研究。 (三)兔腹部迷走神经外周端的降压效应可能通过中枢和局部两种因素的作用而实现。中枢的作用系经内脏大神经传入,而外周的局部作用既不能被阿托品所取消,也不能被依色林所加强,但却能为抗组织胺药所抑制,其机制还有待进一步阐明。     

家兔侧脑室注射组胺对肺动脉血压的影响

本工作将组胺(HA)注入麻醉家兔侧脑室,观察其对肺动脉血压的影响。结果观察到(1)侧脑室注射HA(50μg)后,肺动脉压和心输出量出现升高、降低和先降后升三种变化,但以升高反应较为多见。发生上述反应时,颈动脉压升高,心率减慢。(2)切断两侧颈部迷走神经或用心脏人工起搏固定心率后,肺动脉压和心输出量均不再下降而出现恒定的升高反应。静脉注射酚妥拉明可部分阻断HA引起的肺动脉和颈动脉升压反应,但不能阻断心输出量的升高。静脉注射心得安能完全阻断HA引起的心输出量升高,但对肺动脉和颈动脉的升压反应无影响。静脉注射六甲双铵或联合应用酚妥拉明和心得安可完全消除HA引起的肺动脉压、颈动脉压和心输出量的升高反应。(3)HA的心血管效应可被H_1受体阻断剂扑尔敏阻断,但不能被H_2受体阻断剂甲氰咪胍阻断。 实验结果表明:家兔侧脑室注射HA后,在中枢H_1受体的介导下,可通过交感神经使心输出量增加,肺血管和外周血管收缩,因而肺动脉压和颈动脉压上升;也可通过迷走神经使心率减慢。而HA引起的肺动脉压下降则是继发性的,是由于心率减慢,心输出量减少所致。     

家兔第四脑室注射乙酰胆碱对肺动脉血压的影响

本工作将乙酰胆碱(ACh)注入麻醉家兔第四脑室,观察其对肺动脉血压的影响。结果发现(1)脑室注射50—100μg ACh后,肺动脉压和颈动脉压均下降。与此同时心率也出现一过性减慢。(2)切断两侧颈部迷走神经,ACh不再使心率减慢,但其降低肺动脉压和颈动脉压的作用不受到任何影响。(3)预先由第四脑室注射阿托品,可阻断AGh引起的肺动脉降压反应和颈动脉降压反应。(4)第四脑室注射六甲双铵或酚妥拉明,均不能阻断这二个降压反应。(5)第四脑室注射心得安不能阻断ACh引起的肺动脉降压反应,但能阻断ACh降低颈动脉压的作用。 实验结果表明:脑中ACh水平升高可通过激活胆碱能M-受体引起肺动脉压和颈动脉压下降;在ACh引起的颈动脉降压反应的中枢环节中有肾上腺素能β-受体活动参与;而且ACh降低肺动脉压和颈动脉压的作用不是通过迷走神经实现的,可能是由于延髓交感缩血管中枢紧张性降低所造成的。     

伏核对心血管活动的作用及其与阿片肽的关系

本文对乌拉坦麻醉大鼠采用电刺激伏核和脑内微量注射等方法,观察伏核对血压、心率的影响:(1)电刺激伏核具有明显的血压降低和心率减慢作用。(2)红藻氨酸微量注入伏核可消除上述反应。(3)伏核内注射纳洛酮可阻断电刺激伏核的心血管抑制反应(简称电刺激效应);μ受体激动剂DAGO微量注入伏核也能引起血压降低和心率减慢,减少幅度与电刺激效应相似,而κ受体激动剂U-50无此作用。(4)电刺激伏核时于蓝斑内记录到抑制性自发电活动,频率减慢,波幅交大、变宽。(5)切除颈部双侧迷走神经消除了电刺激伏核的心率变化,但降压反应依然存在。以上结果提示:伏核内某些神经元与心血管活动有关,并且至少涉及阿片肽能神经元及μ阿片受体。蓝斑和迷走神经可能参与上述心血管抑制反应。     

电刺激膈神经中枢端对家兔动脉血压和血浆血管紧张素Ⅱ及肾神经传出放电的影响

电刺激家兔膈神经中枢端（ＳＣＰＮ）可引起动脉血压下降,此降压反应不能被剪断双侧颈迷走神经或静脉注射阿托品１ｍｇ／ｋｇ所阻断;但可以被静脉注射酚妥拉明２．０ｍｇ／ｋｇ或静脉注射心得安１．５ｍｇ／ｋｇ部分阻断。去除缓冲神经后,其降压反应更明显。降压反应后ｌｍｉｎ血浆血管紧张素Ⅱ水平降低（Ｐ＜０．０５）,肾神经传出放电（ＲＮＤ）减少（Ｐ＜０．０１）,上述结果表明,膈神经的感觉纤维参与血压调节。     

电刺激膈神经中枢端对家兔动脉血压和血浆血管紧张素Ⅱ…

电刺激家兔膈神经中枢端（ＳＣＰＮ）可引起动脉血压下降,此降压反应不能被剪断双侧颈迷走神经或静脉注射阿托品１ｍｇ／ｋｇ所阻断;但可以被静脉注射酚妥拉明２．０ｍｇ／ｋｇ或静脉注射心得安１．５ｍｇ／ｋｇ部分阻断。去除缓冲神经后,其降压反应更明显。降压反应后１ｍｉｎ血浆血管紧张素Ⅱ水平降低（Ｐ＜０．００５）,肾神经传出放电（ＲＮＤ）减少（Ｐ＜０．０１）,上述结果表明,膈神经的感觉纤维参与血压调节。     

家兔肺动脉内注射乙酰胆碱对肺动脉血压的影响

在65只氨基甲酸乙酯麻醉的兔,向肺动脉内注射2—4μg乙酰胆碱(ACh),可使颈动脉压出现短暂下降,回升时,肺动脉压可出现升压或降压两种反应,但以升压反应较为多见。发生这两种反应时,心率无明显变化。上述颈动脉降压反应、肺动脉升压和降压反应均能被阿托品阻断。乙酰胆碱引起的肺动脉升压反应可以被胆碱能N-受体阻断剂六甲双铵阻断,亦可被α-受体阻断剂酚妥拉明部分逆转。β-受体阻断剂心得安能部分逆转乙酰胆碱降低颈动脉压的作用,但对乙酰胆碱升高或降低肺动脉压的作用无任何影响。 结果表明,当血液中乙酰胆碱水平升高使肺动脉压下降主要是由于乙酰胆碱直接使肺血管平滑肌舒张。而促使肺动脉压上升的原因,是由于乙酰胆碱一方面直接使肺血管平滑肌收缩;另一方面还可激活交感神经节中N-受体,促进去甲肾上腺素释放,后者与α-受体结合而引起肺血管收缩所致。     

家兔第四脑室注射P物质对肺动脉压和颈动脉压的影响

本工作将P物质(SP)注入麻醉家兔第四脑室,观察其对肺动脉压和颈动脉压的影响。结果观察到:(1)脑室注射SP后,肺动脉压升高或降低,颈动脉压上升,心率减慢。(2)切断肺动脉压下降组家兔的两侧颈部迷走神经,再ivt.SP,则引起肺动脉压的升高,降心率反应则明显减弱。(3)预先用酚妥拉明或α_1受体阻断剂哌唑嗪均可阻断SP引起的肺动脉和颈动脉升压反应。(4)α_2受体阻断剂育亨宾或纳洛酮均可增强这二个升压反应。(5)心得安对这二个升压反应无明显影响。(6)SP的心血管效应可被SP受体拮抗剂[D-pro~2.D-Trp~(7.9)]-SP阻断。 实验结果表明:脑中SP升高可通过SP受体引起肺动脉压和颈动脉压上升,心率减慢;在SP引起的加压反应的中枢环节中有肾上腺素能α_1受体活动参与;中枢肾上腺素能α_2受体系统和内啡肽系统对传递SP中枢加压作用的路径有抑制性的调制作用。看来,SP与儿茶酚胺及阿片样物质一起参与脑干对血压的调节。     

室旁核在刺激猫肾神经传入纤维引起的血压效应中的作用

本研究的目的是在氯醛糖麻醉、颈动脉窦、主动脉弓去神经和切断迷走神经的猫中探讨室旁核和室旁核α_1肾上腺素受体在刺激肾神经传入纤维引起的升压反应中的作用。刺激肾神经中枢端可引起动脉血压明显升高。这种血压升高由两个成分组成。第一成分可被植物性神经阻断剂六烃季铵和阿托品所阻断,第二成分不能被植物性神经阻断剂所阻断。双侧室旁核毁损后,植物性神经阻断前、后刺激肾神经中枢端引起的升压反应都明显减弱。侧脑室和室旁核微量注射α_1肾上腺素受体拮抗剂哌唑嗪,可显著抑制刺激肾神经传入纤维引起的升压反应。这些结果表明,室旁核和中枢的,尤其在室旁核的α_1肾上腺素受体在刺激肾神经传入纤维引起的升压反应中起重要作用。     

刺激家兔肾内感受器和肾传入神经的血流动力学效应

在39只麻醉家兔观察刺激肾脏机械和化学感受器以及电刺激肾传入神经的血流动力学效应。增加输尿管压8—22mmHg 及经输尿管向肾盂内逆向灌注 NaCl(1.0 mol/L)及 KCl(0.15mol/L)溶液时,引起平均动脉压(MAP)和心率(HR)下降;切断双侧缓冲神经后,MAP 降低更为显著。电刺激肾传入神经时,HR 减慢,MAP、肠系膜动脉和后肢动脉灌流压降低,左心室收缩压及其微分值下降,心输出量(CO)和总外周阻力(TPR)减小;切断双侧窦神经和减压神经后,除 HK、CO 和 TPR 外,其余各血流动力学指标的减弱更为显著。由此提示,动脉压力感受器反射对肾传入神经激活的心血管效应有缓冲作用。     

Biocybernetic studies on reflectory heart modification in the rabbit]

In rabbits the depressor nerves and cardiac vagal branches were stimulated. Their actions on heart rate, atrio-ventricular conduction time, myocardial action potential and mean central blood pressure were recorded. The frequency-effect characteristics of the chronotropic, dromotropic and electrotropic actions on the heart, resulting from afferent and efferent nerve stimulation, are compared. The participation of each of the depressor nerves in their total effects on heart rate and blood pressure is studied. Time courses of heart rate and blood pressure decrease by afferent and efferent nerve stimulation with sinusoidally modulated pulse rates are presented. The results are discussed with respect to the different dynamics of blood pressure and heart rate control. It is concluded that at least two mechanisms are involved in blood pressure control by the depressor nerves: 1. Decrease of vascular resistance by lowering the sympathetic tone. 2. Decrease of heart rate by enhancing the cardiac vagal activity. It is suggested that the parasympathetic control unit compensates rapid disturbances, whereas the slow-acting sympathetic vascular mechanism exerts a long-time pressure control of high efficiency.     

Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits.

Substance P (SP) is abundant in the carotid sinus nerve (CSN) and has been implicated in baro- and chemoreceptor reflexes. We examined the effect of SP on blood pressure, heart rate, phrenic nerve activity, hindlimb perfusion pressure, and cardiac contractile strength in urethane-anesthetized rabbits with bilaterally cut cervical sympathetic, vagus, and aortic depressor nerves. Retrograde simultaneous injection of SP (0.5-2.7 micrograms/kg in 0.2-0.3 ml saline) into both carotid sinus areas via the internal carotid arteries decreased blood pressure (by 56%), heart rate (by 13%), cardiac contractility (by 25%) and phrenic nerve activity (by 77%). The effect on hindlimb perfusion pressure was variable. There was both a reflex effect and direct hindlimb vasodilation. In another group of rabbits, the carotid sinus areas were vascularly isolated and perfused with SP (0.19 micrograms/min dissolved in Locke's solution) or Locke's solution alone for 5 min. While carotid sinus perfusion pressure was maintained in the range of 80-120 mmHg, mean arterial blood pressure, heart rate, and unit activity from the CSN were recorded. SP increased the activity of 11 of 18 baroreceptor fibers and inhibited all of 20 chemoreceptor fibers. SP decreased mean arterial blood pressure and heart rate, but the changes were less than those obtained with injection of SP into nonisolated carotid sinus arteries because systemic effects of SP, which in some cases counteracted the reflex effects, were eliminated.     

蓝斑对迷走─心血管反射的影响

实验用家兔３６只,采用低频（５－８Ｈｚ）和高频（５０－１００Ｈｚ）电流刺激颈部迷走神经中枢端（ＶＡＳ）,建立迷走－减压和迷走－升压反射,两种频率电刺激均导致肾交感神经传出活动（ＲＳＡ）减少。以迷走－血压反射和迷走－交感反射为指标,连续电流刺激蓝斑（ＬＣ）或ＬＣ微量注射谷氨酸钠均抑制迷走－血压反射和迷走－交感反射。而连续电流刺激ＬＣ或ＬＣ微量注射谷氨酸钠本身均引起平均动脉血压升高和ＲＳＡ增加。本文对新近提出的对ＬＣ整体功能认识的理论,结合本文的结果进行了讨论     

Group III muscle afferents evoke reflex depressor responses to repetitive muscle contractions in rabbits

Repetitive-twitch contraction of the hindlimb muscles in anesthetized rabbits consistently evokes a reflex depressor response, whereas this type of contraction in anesthetized cats evokes a reflex pressor response in about one-half of the preparations tested. Rapidly conducting group III fibers appear to comprise the afferent arm of the reflex arc, evoking the depressor response to twitch contraction in rabbits because electrical stimulation of their axons reflexly decreases arterial pressure. In contrast, electrical stimulation of the axons of slowly conducting group III and group IV afferents reflexly increases arterial pressure in rabbits. In the present study, we examined the discharge properties of group III and IV muscle afferents and found that the former (i.e., 13 of 20), but not the latter (i.e., 0 of 10), were stimulated by 5 min of repetitive-twitch contraction (1 Hz) of the rabbit triceps surae muscles. Moreover, most of the group III afferents responding to contraction appeared to be mechanically sensitive, discharging in synchrony with the muscle twitch. On average, rapidly conducting group III afferents responded for the 5-min duration of 1-Hz repetitive-twitch contraction, whereas slowly conducting group III afferents responded only for the first 2 min of contraction. We conclude that rapidly conducting group III afferents, which are mechanically sensitive, are primarily responsible for evoking the reflex depressor response to repetitive-twitch contractions in anesthetized rabbits.     

Canine vagus nerve stores cholecystokinin-58 and -8 but releases only cholecystokinin-8 upon electrical vagal stimulation

Cholecystokinin-58 has been shown to be the major form of cholecystokinin (CCK) released to the circulation upon lumenal stimulation of the small intestine in humans and dogs. In anesthetized dogs, electrical vagal stimulation evokes pancreatic exocrine secretion that is in part mediated through the release of CCK. We studied the molecular form of CCK stored in canine vagus nerves and that released into circulation upon electrical vagal stimulation. Gel filtration and radioimmunoassay of the water and acid extracts of canine vagus nerves indicated CCK-8 (35%) and CCK-58 (65%) as the major molecular forms in the vagus nerve. Both forms of CCK isolated from the vagal extracts were equally bioactive as the standard CCK-8 and CCK-58, respectively, in stimulation of amylase release from isolated rat pancreatic acini. Analysis of plasma collected after electrical vagal stimulation indicated that CCK-8 is the only form released into the circulation. The release of CCK-8 upon electrical vagal stimulation was not affected by application of lidocaine to the upper small intestinal mucosa, suggesting that it was released from vagal nerve terminals.     

Are prostaglandins involved in atrial natriuretic peptide mechanisms of cardiovascular control?

Atrial natriuretic peptide (ANP) can excite cardiac nerve endings and invoke a decrease in arterial blood pressure and a reduction in renal sympathetic nerve activity. Our laboratory has previously demonstrated that this renal depressor reflex was invoked by systemic injection of ANP and not by the direct application of ANP to the epicardium, a major locus for vagal afferents. We now examine whether inhibition of prostaglandin synthesis impairs reflex responses that are normally associated with ANP injections. Renal sympathetic nerve activity, arterial blood pressure, and heart rate were recorded in anesthetized rats. Indomethacin was used to inhibit prostaglandin synthesis through the cyclooxygenase pathway. The ANP-mediated decrease in arterial blood pressure and renal sympathetic nerve activity, observed when prostaglandin synthesis was inhibited, did not differ significantly from the decreases observed in these parameters when prostaglandin synthesis was not inhibited. Heart rate remained unchanged. Our results suggest that the sympatho-inhibitory effects of ANP do not require prostaglandins as intermediary compounds.     

缓冲神经在刺激兔下丘脑诱发室性期前收缩中的作用

1.静脉注射氰化钾(0.3mg/kg)可引起血压升高和室性心律失常,并能使刺激下丘脑诱发的室性期前收缩增多。去除双侧窦神经后,上述现象消失。2.刺激降压神经时,刺激下丘脑诱发的室性期前收缩显著减少。3.切断双侧缓冲神经后短时内,刺激下丘脑诱发的室性期前收缩极度增多,并且不易被躯体传入冲动所抑制。二小时后,这种室性期前收缩减少,且可为刺激腓深神经所抑制。4.电刺激延髓中线区不仅可以降低血压,而且能减弱刺激下丘脑诱发的升压反应、抑制刺激下丘脑诱发的室性期前收缩。损毁该区后,刺激腓深神经不再能抑制刺激下丘脑诱发的室性期前收缩。5.上述结果表明:化学感受性反射能易化刺激下丘脑诱发的室性期前收缩,而压力感受性反射可以抑制这种室性期前收缩,但躯体传入冲动对这种心律失常的抑制作用并不依赖于缓冲神经的存在,而有赖于延髓中线核群的完整性。     

刺激肾神经传入纤维的降压反应与颈动脉窦压力感受性反射的相互作用

在麻醉兔,研究了刺激肾神经传入纤维与颈动脉窦压力感受性反射在减压反射中的相互作用。电刺激肾神经传入纤维引起平均动脉压(MAP)下降,下降程度在一定范围有赖于刺激频率。当颈动脉窦被隔离和主动脉神经切断后,随着颈动脉窦内压逐渐升高,刺激肾神经传入纤维引起的减压反应不断减弱。在45至135mmHg 之间的7个颈动脉窦内压(ISP)水平,刺激肾神经传入纤维,并画出刺激前和刺激时的 ISP-MAP 关系曲线。在颈动脉窦内压为75至105mmHg 之间,刺激肾神经传入纤维显著降低 ISP-MAP 关系曲线的斜率和对ISP 的平均动脉压反应范围。这些结果提示:(1)颈动脉窦压力感受器的传入冲动可调制刺激肾神经传入纤维的降压反应,在一定范围内与颈动脉窦内压呈反比;(2)刺激肾神经传入纤维明显减弱颈动脉窦的压力感受性反射。