针刺对急性实验性高血压抑制效应的机制分析

本工作在清醒犬上进行,介绍了两种间接测量动脉血压的方法。观察到电针“足三里”穴对正常动物的血压、心率、呼吸并无显著影响。当静脉内匀速注射去甲肾上腺素造成急性实验性高血压时,电针具有显著的降压效应,对心率和呼吸则无明显影响。电针产生降压效应时,内脏血管舒张,血流量增加,而心输出量并不减少,且降压效应不被阿托品阻断。在实验性高血压时静脉注射吗啡可产生与电针相类似的降压效果,静脉注射纳洛酮可阻断电针的降压作用。结果表明:电针对实验性高血压的降压效应主要是交感缩血管中枢紧张性受抑制使外周血管舒张而产生的,此种抑制效应与电针时中枢内产生的内源性鸦片样物质有关。     

脑内微量注射吗啡、纳洛酮对针刺降压作用的影响

在清醒犬的中脑中央灰质、海马背侧、乳头体上区等中枢部位微量注射生理盐水(2微升/2分钟),对血压、心率无明显影响,此时电针“足三里”穴对匀速注射去甲肾上腺素所致的实验性高血压具有显著的降压效应。在这种高血压的基础上,在以上三个部位微量注射吗啡(4微克/2微升/2分钟)可见血压短暂下降后又回升到原高血压水平,心率无显著变化。在这些部位微量注射纳洛酮后(4微克/2微升/2分钟)则以上电针降压效应消失。而在大脑顶叶内侧皮层微量注射吗啡对血压、心率无明显影响;在该处微量注射纳洛酮后,电针对实验性高血压仍有明显的降压作用。结果表明:电针对交感缩血管中枢的抑制与电针时中枢内产生的内(脑)啡肽对中脑中央灰质、海马、乳头体上区等部位鸦片受体的激活有关。     

刺激家兔腓深神经对颈动脉体化学感受性升压反射的调整作用

在麻醉、制动和人工通气的79只家兔上观察到,由颈动脉内注射氰化钠(NaCN)引起的颈动脉体化学感受性升压和肾交感放电增强反应(简称颈动脉体反应),在刺激腓深神经模拟电针“足三里”穴位时发生明显改变。此种改变与腓深神经刺激前颈动脉体反应的强度有关。在吸入气中加入CO_2或切断双侧颈迷走神经以提高心血管中枢活动水平时,颈动脉体反应增强,此时刺激腓深神经可使此反应减弱(P<0.01)。在迷走神经完整、增加潮气量使血液CO_2分压降低,使颈动脉体反应减弱时,刺激腓深神经可使颈动脉体反应增强(P<0.01)。上述结果表明,刺激腓深神经,对颈动脉体化学感受性心血管反应具有调整作用,这种作用与心血管中枢反应性密切相关。而后者又受到迷走神经传入冲动、PaCO_2水平和麻醉深度调制。     

不同血压水平下刺激腓深神经对兔肾交感神经放电的影响

本实验观察了53例兔在不同血压水平下不同参数的腓深神经刺激对肾交感神经活动的影响。物在正常血压时,用低强度电流(3V,0.15—0.3mA,12Hz,0.5ms)刺激腓深神经可明显抑制肾交感冲动发放,静脉注射纳洛酮可以阻断此抑制效应;而用中等强度电流(10V,0.5—0.8mA)刺激腓深神经对肾交感活动没有明显抑制效应。当静脉匀速注射硝普钠使动物血压降低、肾交感冲动增加时,用中等强度刺激腓深神经可使肾交感冲动发放进一步增多,而用低强度刺激对肾交感活动无显著影响。静脉注射东莨菪碱(0.25mg/kg)可阻断低血压时刺激腓深神经引起的肾交感兴奋效应,但静脉注射纳洛酮(0.4mg/kg)却不能阻断。又当静脉匀速注射去甲肾上腺素造成动物较高血压时,肾交感冲动减少,用上述二种强度刺激腓深神经均使肾交感活动进一步受到明显抑制,此抑制效应可被静脉注射纳洛酮阻断,但不受东莨菪碱的影响。实验结果表明:刺激腓深神经引起的不同肾交感活动反应与所用刺激参数及动物血压水平和肾交感活动水平有关。刺激腓深神经引起的交感活动减弱或增强的反应,其神经机制可能不完全相同。前者可能有阿片受体的参与,而后者可能是胆碱能受体起着较重要的作用。     

电针对清醒家兔压力感受性反射的重调定

实验在22只清醒家兔上进行。分别用苯肾上腺素(20μg/kg,iv)和硝普钠(30μg/kg,iv)改变血压,同时记录心率,以血压-心率关系为指标,观察电针“足三里”穴(4mA,3Hz,0.5ms,持续20min)对压力感受性反射的重调定作用。电针时,基础血压及心率无明显改变,但血压-心率关系回归直线的斜率明显加大,表明压力感受性反射的敏感性增强。用记录神经动作电位的方法证明,电针“足三里”时主要兴奋Ⅰ、Ⅱ、Ⅲ类纤维。上述结果提示,电针可通过兴奋躯体传入纤维对压力感受性反射重调定,增高压力感受性反射的敏感性,故能提高压力感受性反射纠正异常血压的能力。     

硝普钠造成犬低血压时电针升压作用的机制分析

本工作观察到给清醒犬静脉内匀速注射扩血管药硝普钠可造成稳定的急性实验性低血压,电针相当于“足三里”或“内关”穴部位对此实验性低血压具有显著的升压作用,而对心率和呼吸频率无明显影响。在麻醉动物身上,电针对此类实验性低血压仍可产生显著的升压作用。电针产生升压作用时,心输出量增加,肾血流量减少,而肠系膜上动脉及股动脉血流量变化不显著。还观察到电针可使实验性低血压部分的血压-心率曲线右移,斜率增大。实验性低血压时,静脉注射纳洛酮不能阻断电针的升压作用,而注射阿托品或东茛菪碱后给予电针不再出现升压效应。实验结果表明:电针对舒血管药物造成的急性实验性低血压具有明显的升压作用,此升压作用仍可在麻醉动物身上产生,并与电针时中枢内胆碱能系统的激活有关,而心输出量增加和肾血流量减少在电针升压效应中起一定作用。     

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。     

清醒大鼠室旁核灌流谷氨酸受体阻断剂对压力感受性反射的影响

目的:探讨下丘脑室旁核(PVN)内谷氨酸参与压力感受性反射中枢调节的神经化学机制。方法:在清醒大鼠,用脑部微量透析法和高效液相色谱法观察静脉注射苯肾上腺素诱发压力感受性反射对PVN区谷氨酸含量的影响;NMDA受体阻断剂MK-801或非NMDA受体阻断剂CNQX直接灌流PVN区并诱发压力感受性反射,进一步探讨PVN区谷氨酸对压力感受性反射的作用。结果:①静脉注射苯肾上腺素诱发压力感受性反射时,PVN内的谷氨酸含量迅速升高到注射前的384.82%±91.77%(P<0.01)。②PVN区灌流谷氨酸受体阻断剂MK-801或CNQX,同时诱发压力感受性反射,其血压升值明显减少,心率降值明显增加(P<0.01),压力感受性反射的敏感性(△HR/△MAP)明显增加(P<0.01)。结论:PVN内的谷氨酸可能通过离子型谷氨酸受体参与压力感受性反射的中枢调节,而且此调节作用可能是抑制性的。     

躯体传入对肾交感神经活动及某些内感受性反射的影响

本工作记录家兔的肾交感神经冲动、动脉血压和心率,观察到以低频率、低强度刺激腓深神经(强度3伏,频率12次/秒,波宽0.5毫秒,持续20分钟),可以显著抑制肾交感神经的放电活动,但对血压和心率无显著影响。刺激腓深神经后吸10%氧引起缺氧时的交感兴奋和升压反射以及夹闭一侧颈总动脉引起的升压反射均受到抑制。这些抑制现象可因静脉注射纳洛酮(0.4毫克/公斤)而被翻转。结果表明:低频低强度的腓深神经刺激可抑制交感缩血管中枢及升压反射,这种抑制效应和内源性鸦片样物质的释放有关。     

内源性可乐宁样物质

可乐宁(clonidine)是一种人工合成的α_2受体激动剂,可抑制中枢交感神经的传出冲动,产生强大的降压效应,已被广泛应用于临床各型高血压的治疗。去甲肾上腺素和α-甲基多巴也是中枢α受体特异性配基;它们的作用与可乐宁不同。例如,网状外侧核内注射微量可乐宁,可引起明显的降压作用;但注射去甲肾上腺素或α-甲基多巴则不能引起。去     

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。     

伏核在躯体传入冲动抑制防御性心血管反应中的作用及机制

损毁伏核可明显削弱电刺激腓深神经（ＤＰＮ）对兴奋下丘脑背内侧核诱发的升压反应和心肌缺血的抑制作用（Ｐ＜０．０５,Ｐ＜０．０１）。电刺激伏核可引起明显的降压效应。中脑中央灰质腹侧部（ｖＰＡＧ）微量注射纳洛酮可明显衰减伏核的减压效应;损毁ｖＰＡＧ甚至可翻转伏核的减压效应,引起轻度升压（Ｐ＜０．０１）。损毁弓状核后伏核的减压效应基本消失,弓状核内微量注射纳洛酮明显衰减伏的的减压效应。故ＤＰＮ传入冲动可能     

Systemic and renal hemodynamic responses to vascular blockade of vasopressin in conscious dogs with ascites

A role for arginine vasopressin has been implicated in the compensatory control of arterial blood pressure in several animal models with reported increases in plasma levels of arginine vasopressin. A threefold elevation in plasma vasopressin has been reported in conscious dogs following constriction of the inferior vena cava. In the present study, infusion of the arginine vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine] Arg8-vasopressin into conscious dogs with chronic caval constriction did not decrease mean arterial blood pressure. However, the dose of infused antagonist completely blocked the pressor response to 2 micrograms of exogenous vasopressin. Also the antagonist produced no effect on heart rate, plasma renin activity, or urinary volume and electrolyte excretions. A slight, transient increase (P less than or equal to 0.05) was observed in creatinine clearance and in PAH clearance following antagonist infusion, suggesting a possible decrease in renal vascular resistance. These data suggest that the direct vasoconstrictor actions of vasopressin contribute minimally, if at all, to blood pressure maintenance following chronic caval constriction. Alternatively, blockade of endogenous vasopressin receptors at the level of peripheral arterioles may have resulted in no depressor response due to a masking of this response by other compensatory hormonal and neural pressor systems.     

Depressor reactions to sural nerve stimulation in intact unanesthetized cats]

Changes in the arterial pressure, in the heart and respiratory rate evoked by the gastrocnemuis nerve stimulation were studied on conscious cats before and during intravenous injection of noradrenaline. Stimulation of the gastrocnemius nerve increased the arterial pressure, the heart and respiratory rates. The same stimulation of the nerve during hypertension caused by noradrenaline injection led to the fall of arterial pressure and tachycardia. The depressor response failed to change under the effect of the beta-adrenoreceptor block and disappeared after the m-cholinoreceptor block with methylatropine. The depressor response was absent in the unanesthetized decerebrated cats. It is supposed that the depressor response of the arterial pressure depended on the strong cholinergic vasodilatation, reflexively evoked by stimulation of the motor nerve in the intact cats.     

Characteristics of the central adrenergic mechanisms regulating arterial pressure in rats with hereditary arterial hypertension

Adrenergic mechanisms of blood pressure regulation were studied in a newly developed strain of rats with inherited stress-provoked arterial hypertension, spontaneously hypertensive rats (SHR) and normotensive Wistar rats. A number of adrenergic agonists (noradrenaline, adrenaline, phenylephrine, clonidine, naphazoline, isoproterenol, dobutamine, Alupent) were infused into the lateral brain ventricle under nembutal anesthesia and the reaction of the peripheral blood pressure was measured. It was shown that blood pressure reactions were similar in rats with inherited stress-provoked arterial hypertension and in SHR but significantly differed from those of normotensive Wistar rats. The data obtained suggest that the development of inherited hypertension was accompanied by changes in alpha 1 to alpha 2 adrenoreceptor ratio in pressor and depressor brain regions. A decrease in the depressor effect after stimulation of beta 1 and beta 2 receptors has been also observed.     

Super-long latent somato-sympathetic response in non-anesthesized decerebrate frogs

Somato-sympathetic reflex responses were studied by recording the activity of the renal sympathetic efferents following excitation of sciatic nerve A-afferents in immobilized decerebrated frogs before and during viadril-induced anesthesia. Apart from A-response reported in anesthetized frogs and consisting of excitatory and inhibitory components, in non-anesthetized frogs reflex discharge with a latency over 2 sec was revealed. Unlike the former one, this response disappeared after intravenous injection of viadril. In the same frogs intravenous injection of viadril converted pressor reflexes in response to stimulation of sciatic nerve A-afferents into depressor ones. A-response with superlong latency is assumed to reflect the excitation of those central structures that are responsible for the development of pressor reflexes to somatic A-fiber stimulation. In this respect the described somato-sympathetic A-response seems to be analogous to the very late A-response in the mammals.     

充胀犬胸部降主动脉所致的升压效应

在17只麻醉开胸犬,观察局部充胀胸部降主动脉(TDA)对心血管活动的影响。主要结果如下:1.充胀 TDA 引起心率、心肌收缩力、肾及股薄肌灌注压和全身动脉血压增加;TDA 局部去神经后反应消失,表明上述心血管效应系 TDA 受牵张刺激引起的正反馈性神经反射现象。2.切断动物两侧颈迷走神经和窦神经后,充胀 TDA 引起的心血管效应增大。3.用心得安(1mg/kg)消除心脏的β-效应后,充胀 TDA 引起的升压反应有所减小;用酚妥拉明(3mg/kg)阻断血管的α-受体效应后,多数动物即不再出现血压增高,从而提示充胀TDA 时的血压升高主要是反射性外周阻力增加所致。在缓冲神经完整的条件下,上述 TDA加压效应是存在的,但主动脉弓和颈动脉窦缓冲反射对其有对抗作用。     

刺激腓深神经对低血压或休克狗心血管活动的影响

实验在麻醉狗中进行。静脉内匀速注射硝普钠时,平均动脉压和左心室收缩压明显降低,左心室dp/dt_(max)、-dp/dt_(max)和心力环面积均明显减小。此时电刺激一侧腓深神经可使动脉血压和左心室收缩压明显升高,dp/dt_(max)和心力环面积也显著增加。停止刺激后,动脉血压和左心室收缩压逐渐回向刺激前的水平。停止注射硝普钠5～15分钟后,上述各项观察指标基本恢复到注药前的水平。在用大肠杆菌内毒素造成休克的狗中,电刺激一侧腓深神经,也能使平均动脉压和左心室收缩压升高,同时dp/dt_(max)、-dp/dt_(max)和肠系膜血管阻力明显增高,但肾血管阻力增加不明显。本实验结果与以往的实验资料一起表明,在用扩血管药造成低血压时,躯体神经刺激引起的升压效应似乎以心肌收缩力增加为主;而在内毒素休克时,躯体神经刺激可通过改善心肌收缩功能和增加内脏血管阻力而引起升压作用。     

刺激家兔腹部迷走神经外周端引起的降压作用

本文对电刺激家兔腹部的迷走神经外周端所引起的降压反应进行了研究。在121只家兔中的实验结果表明:电刺激腹部迷走神经外周端可引起动脉压、小肠和后肢的灌流压同时降低,而心率则无明显变化。这一降压反应发生时,小肠静脉血中的组织胺含量较刺激前明显升高,然后恢复;将小剂量的组织胺 H_1受体阻断剂扑尔敏、非乃根和 H_2受体阻断剂甲氰咪胍(Cimetidine)分别注入肠系膜上动脉均能减弱刺激腹部迷走神经外周端引起的动脉压和小肠灌流压的降低。心得安能削弱此降压反应,而阿托品无效;切断两侧内脏大神经能显著削弱刺激腹部迷走神经外周端引起的降压反应。此残余的降压反应在注入抗组织胺剂后完全消失。由此推论,刺激家兔腹部迷走神经外周端引起的降压反应是通过中枢和外周两方面因素的作用,使血管舒张,外周阻力降低而实现的。     

Hypobaric Intermittent Hypoxia Attenuates Hypoxia-induced Depressor Response

Background

Hypobaric intermittent hypoxia (HIH) produces many favorable effects in the cardiovascular system such as anti-hypertensive effect. In this study, we showed that HIH significantly attenuated a depressor response induced by acute hypoxia.

Methodology/Principal Findings

Sprague-Dawley rats received HIH in a hypobaric chamber simulating an altitude of 5000 m. The artery blood pressure (ABP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in anesthetized control rats and rats received HIH. The baseline ABP, HR and RSNA were not different between HIH and control rats. Acute hypoxia-induced decrease in ABP was significantly attenuated in HIH rat compared with control rats. However, acute hypoxia-induced increases in HR and RSNA were greater in HIH rat than in control rats. After removal of bilateral ascending depressor nerves, acute hypoxia-induced depressor and sympathoexcitatory responses were comparable in control and HIH rats. Furthermore, acute hypoxia-induced depressor and sympathoexcitatory responses did not differ between control and HIH groups after blocking ATP-dependent K⁺ channels by glibenclamide. The baroreflex function evaluated by intravenous injection of phenylephrine and sodium nitroprusside was markedly augmented in HIH rats compared with control rats. The pressor and sympathoexcitatory responses evoked by intravenous injection of cyanide potassium were also significantly greater in HIH rats than in control rats.

Conclusions/Significance

Our findings suggest that HIH suppresses acute hypoxia-induced depressor response through enhancement of baroreflex and chemoreflex function, which involves activation of ATP-dependent K⁺ channels. This study provides new information and underlying mechanism on the beneficiary effect of HIH on maintaining cardiovascular homeostasis.