大鼠延髓A5区降压、降心率效应的机制及其与A1区之比较

在与上一篇论文(关于A_1区)相同的条件下,(1) 用谷氨酸钠兴奋大鼠A_5区,和A_1区类似,也产生明显的降压、降心率效应。(2) 切断双侧颈迷走神经也明显衰减兴奋A_5区的心血管作用。(3) 将不同受体阻断剂注入延髓头端腹外侧区对兴奋A_5区引起的降压,降心率反应之影响,与A_1区比较有所不同:酚妥拉明、心得安、纳洛酮和荷包牡丹碱均能明显衰减A_5区的降压、降心率效应(心得安和荷包牡丹碱甚至反转之),表明除α-,β-,GABA受体之外,阿片受体也中介A_5区的降压降心率作用。     

谷氨酸钠兴奋室旁核引起的升压效应及其与蓝斑-升压反应和A_1-降压反应间的关系

将L-谷氨酸钠(Glu)注入乌拉坦麻醉、箭毒化、人工呼吸大鼠的室旁核(NPV)或蓝斑内引起升压反应。蓝斑升压反应可被双侧室旁核内预先注射酚妥拉明或心得安明显衰减;双侧室旁核内预先注射酚妥拉明或荷包牡丹碱还可使Glu兴奋延髓A_1区引起的降压反应减小,但注射心得安对A_1-降压反应无明显影响。以上结果提示蓝斑-升压反应和A_1-降压反应均部分通过NPV实现,A_1降压过程中可能有NPV内GABA能抑制性中间神经元参与。     

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。     

臂旁核对心血管活动的调制及其与延髓头端腹外侧区的机能联系

乌拉坦浅麻、箭毒制动大鼠,人工呼吸维持下,谷氨酸钠微量注入或电刺激臂旁核具有明显的升高血压和加快心率作用,腹侧和背侧臂旁核(NPV和NPD)的效应相似。谷氨酸钠兴奋NPV和NPD分别使血压上升至注射前的125.1±3.8％和123.9±2.1％,心率加快至114.2±2.6％和109.4±0.8％,与相应生理盐水对照组相比较均P<0.01。所用电刺激引起的效应,其幅度与化学刺激引起者相近。酚妥拉明注入双侧延髓头端腹外侧区(RVL)能阻断谷氨酸钠兴奋NPV,NPD对心血管的效应,但不能阻断电刺激的效应,这表明臂旁核神经元的升压和加快心率作用是通过RVL及其内的α-肾上腺素受体实现的;臂旁核内另有过路的加压、加速心率纤维,它们的效应则可能是通过RVL内的其他受体,或甚至通过RVL外的其他脑区起作用的。     

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。     

臂旁核和延髓头端腹外侧区在黑质升压效应中的作用

本实验室观察到黑质具有升压效应。用L-谷氨酸钠微量注入黑质可使血压升高,此效应可被DA受体阻断剂氟哌啶醇(Halo)微量注入臂旁核加压区基本阻断。我们过去的工作证明延髓头端腹外侧区(RVL)及其内的α-受体中介臂旁核的加压效应,本实验将酚妥拉明注入RVL能明显衰减黑质的加压效应,而将Halo注入RVL加压区对黑质加压效应无明显影响。以上结果提示臂旁核-RVL(α-受体)加压系统参与黑质加压效应。     

谷氨酸钠兴奋尾侧导水管周围灰质腹外侧部的升压反应及其在脑干内的传出通路

实验用乌拉坦麻醉、箭毒化、人工呼吸的大鼠,观察到:(1) 胞体兴奋剂L-谷氨酸钠(Glu)注入尾侧导水管周围灰质腹外侧部(PAG)引起明显的加压反应,(2) 该效应可被双侧延髓头端腹外侧(RVL)加压区内注射酚妥拉明或心得安衰减,但不受阿托品注入RVL影响;表明此升压反应是通过RVL及其内的α-及β-受体实现的。(3) RVL内注入心得安也可衰减电刺激腹侧臂旁核(NPV)的加压作用,却不影响Glu注入NPV的升压效应;结合以往的实验结果,提示尾侧PAG腹外侧部的神经元发出的轴突,可能一方面路过臂旁核直接作用于RVL内的β-受体,另一方面可能在臂旁核内换元,然后作用于RVL内的α-受体,而起升压作用。     

大鼠脊髓蛛网膜下腔注射γ-氨基丁酸受体激动剂对降低血压和徐缓心率的作用

给大鼠脊髓蛛网膜下腔注射γ-氨基丁酸(GABA)受体激动剂异鹅羔胺(0.125—0.25μg)能显著降低动物的动脉血压和心率。这种作用可被 GABA 受体阻断剂氯甲基荷包牡丹碱(1.0μg)所翻转,且具有剂量-效应关系。另一种 GABA 受体激动剂 THIP(5μg)以及GABA(500μg)也同样具有降低血压和心率的作用。说明激活脊髓内 GABA 受体具有降低血压和减慢心率的作用。肾上腺素α受体阻断剂育亨宾(30μg)能翻转可乐宁(0.25μg)的降压作用,但不能对抗异鹅羔胺的作用;GABA 受体阻断剂氯甲基荷包牡丹碱可翻转异鹅羔胺的作用,对可乐宁则无效。说明脊髓内异鹅羔胺和可乐宁降血压和减慢心率的作用没有相互的依存关系。     

γ-氨基丁酸、荷包牡丹碱和L-谷氨酸钠对猫和家兔同侧和对侧图形视觉诱发电位的影响

在猫和家兔大脑半球一侧视区17/18交界处施加γ—氨基丁酸(GABA)、荷包牡丹碱和L—谷氨酸钠,以及用氯化钾和冷冻阻遏的方法,记录对侧和同侧皮层相应处图形视觉诱发电位(PVEP)的变化。讨论了GABA、荷包牡丹碱和L—谷氨酸钠对猫和兔的对侧和同侧PVEP的影响。     

γ-氨基丁酸、荷包牡丹碱和L-谷氨酸钠对猫和家兔同侧和对侧图形视觉诱发电位的影响

在猫和家兔大脑半球一侧视区17/18交界处施加γ—氨基丁酸(GABA)、荷包牡丹碱和L—谷氨酸钠,以及用氯化钾和冷冻阻遏的方法,记录对侧和同侧皮层相应处图形视觉诱发电位(PVEP)的变化。讨论了GABA、荷包牡丹碱和L—谷氨酸钠对猫和兔的对侧和同侧PVEP的影响。     

大鼠蓝斑内注入谷氨酸钠的心血管效应

Experiments were done on urethane anesthetized, tubocurarine immobilized and artificially ventilated rats and the following results were observed: (1) Injection of sodium L-glutamate (Glu) into locus coeruleus (LC) could evoke a pressor response, but heart rate was not significantly affected; while depressor and bradycardia effects were observed when injecting into closely adjacent areas. (2) The LC-pressor response decreased after a brain transection caudal to nucleus paraventricularis was made but remained unchanged if the transection was rostral to the nucleus; The LC-pressor response could also be attenuated by preinjection of phentolamine propranolol or atropine respectively into the rostral ventrolateral medulla (RVL). The above results suggest that LC-pressor response is not only mediated by RVL, but also by nucleus paraventricularis.     

An inhibitory role of beta-endorphin in central cardiovascular regulation

The cardiovascular effects of beta-endorphin after administration directly into the nucleus tractus solitarii (NTS) of urethane anaesthetised rats were investigated. Unilateral injection resulted in a dose related fall in mean arterial pressure and heart rate. No change in respiratory frequency was prevented and the bradycardia reduced by pretreatment with locally applied naloxone (10 ng). This dose of the opiate antagonist had no effect on mean arterial pressure or heart rate when administered alone. Antiserum to beta-endorphin (1:50 dilution) caused a rise in pressure and a tendency towards tachycardia on injection into the NTS, while it completely blocked the depressor response and bradycardia induced by beta-endorphin. These results are consistent with the view that a beta-endorphin-like peptide has a depressor role in the central nervous system. The hypotension may result from an effect within the central connections of the baroreceptor reflex arc, probably at the level of the NTS.     

Inhibition of baroreflex vagal bradycardia by activation of the rostral ventrolateral medulla in rats

In stressful conditions, baroreflex vagal bradycardia (BVB) is often suppressed while blood pressure is increased. To address the role of the rostral ventrolateral medulla (RVL), a principal source of sympathetic tone, in inhibition of BVB, we microinjected DL-homocysteic acid (DLH, 6 nmol) into the RVL of chloralose-urethan-anesthetized, sinoaortic-denervated rats to examine the effect on BVB. The BVB was provoked by electrical stimulation of the aortic depressor nerve ipsilateral to the injection sites. DLH microinjection was found to suppress BVB while increasing blood pressure. The inhibition of BVB was observed even during the early phase in which DLH transiently suppressed central inspiratory activity. The inhibition was not affected either by upper spinal cord transection or suprapontine decerebration. Similar results were obtained by microinjection of bicuculline methiodide (160 pmol), a GABA antagonist, into the RVL of carotid sinus nerve-preserved rats due to withdrawal of a tonic GABA-mediated, inhibitory influence including the input from arterial baroreceptors. In conclusion, activation of the RVL inhibits BVB at brain stem level independently of central inspiratory drive.     

Cardiovascular effects of cocaine in anesthetized and conscious rats

This study examined the cardiovascular and respiratory effects of cocaine and procaine in anesthetized and conscious rats. Intravenous cocaine (0.16-5 mg/Kg) elicited a rapid, dose dependent increase in mean arterial pressure of relatively short duration. In pentobarbital anesthetized (65 mg/Kg, i.p.) animals, the pressor phase was generally followed by a more prolonged depressor phase. These effects on arterial pressure were generally accompanied by a significant tachypnea and at larger doses (2.5 and 5 mg/Kg, i.v.), bradycardia. Procaine (0.31 and 1.25 mg/Kg, i.v.) produced similar cardiovascular and respiratory effects (depressor phase, tachypnea) in pentobarbital anesthetized animals. In conscious-restrained animals, both cocaine and procaine (1.25 mg/kg, i.v.) produced pressor responses. The subsequent depressor response was, however, absent in both cases. The cardiovascular effects of cocaine (0.25-1 mg/Kg, i.v.) in urethane anesthetized (1.25 g/Kg, i.p.) animals were essentially similar to those observed in conscious animals. Procaine (1mg/Kg) did not produce any significant cardiovascular effects in urethane anesthetized animals, but did elicit tachypnea. Reserpine pretreatment (10 mg/Kg, i.p.) did not significantly attenuate the pressor response in urethane anesthetized animals. Phentolamine pretreatment (3 mg/Kg, i.v.) did significantly antagonize the pressor effect in urethane anesthetized animals. These results suggest that: the depressor phase is likely due to a interaction between local anesthetic activity (cocaine and procaine) and barbiturate anesthesia, the cardiovascular effects of cocaine in conscious animals are more similar to those observed in urethane anesthetized rats than in pentobarbital anesthetized rats and the pressor effect in urethane anesthetized rats is apparently due to a reserpine resistant catecholaminergic mechanism.     

Beta-endorphin- and GABA-mediated depressor effect of specific electroacupuncture surpasses pressor response of emotional circuit

It has been proved that input of specific electroacupuncture (EA) can activate beta-endorphin(beta-EP)ergic and noradrenergic neurons projecting to the rostral ventrolateral medulla (RVL), the latter acting upon the RVL-GABAergic interneurons, thereby produce depressor effect. The present study further shows that: (1) The EA depressor effect is strong enough to surpass the pressor response of the AC (nucleus amygdaloideus centralis)-emotional circuit, (2) both beta-endorphin (beta-EP) and GABA in the RVL mediate the EA antagonistic effect, (3) the EA effect does not take place in the AC and paraventricular nucleus (two key nuclei besides the RVL, which also have beta-EPergic input) in the emotional circuit.     

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.