脑室内注射甲八肽酰胺(metorphamide)降低血压和减慢心率的机制

清醒大鼠侧脑室注射(icv)甲八肽酰胺(MET)可引起明显的降压和减慢心率作用。用小剂量纳洛酮(0.4mg/kg,ip)预处理可明显拮抗MET的减慢心率作用,但仅部分拮抗其降压作用。大剂量纳洛酮(10mg/kg,ip)才能翻转MET的降压作用。纳洛肼(30μg,icv)不能拮抗MET的减慢心率作用。icv强啡肽1—8可引起降压效应,但对心率无明显影响。此外,家兔icv MET引起降压作用的同时,血浆NA水平明显降低。阿托品可明显拮抗MET的减慢心率作用,但对其降压作用无明显影响。 以上结果提示,MET的减慢心率作用可能由mu 2亚型参与,mu 1亚型则否;而降压作用则由kappa和mu亚型共同参与调节。外周交感活动与MET的降压作用有关,外周迷走神经活动参与MET的减慢心率作用。     

头端延髓腹外侧区血管加压素在刺激中脑dPAG区诱发防御性升压反应中的作用

雄性Sprague－Dawey大鼠,用乌拉坦（70mg/kg）和氯醛糖（30mg／kg）腹腔麻醉。在双侧头端延髓腹外侧区（rVLM区）每侧微量注射血管加压素（AVP）（10pmol／o.1μl）可引起平均动脉压（MBP）升高,心率（HR）变化不明显,每侧微量注射AVP的V1受体拮抗利d（CH2）5[Tyr(Me)2]AVP（0.1nmol／0.1μl）后MBP和HR无明显变化。若预先在rVLM区每侧微量注射AVP的V1受体拮抗剂（0.1nmol/0.1μl）后,再在rVLM区同一部位每侧注入AVP（10pmol／0.1μl）,MBP升高作用消失。电刺激中脑（dPAG区）可诱发防御性升压反应。若在双侧rYLM区每侧微量注射AVP的V1受体拮抗剂（0.1nmol／0.1μl）可对防御性升压反应起部分抑制作用。结果表明,rVLM区内微量注射AVP可引起MBP升高,刺激中脑dPAG区诱发的升压反应均与rVLM区AVP的V1受体的激活有关。     

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.     

β-内啡肽和强啡肽参与可乐宁和去甲肾上腺素的中枢降压效应

大鼠侧脑室注射(icv)可乐宁和去甲肾上腺素(NE)引起血压降低和心率减慢。此效应可被α受体阻断剂酚妥拉明对抗。icvβ-内啡肽抗体、强啡肽抗体或大剂量阿片受体阻断剂纳洛酮也可防止可乐宁和 NE 降压效应的出现;而甲啡肽抗体、亮啡肽抗体或小剂量纳洛酮均无拮抗作用。以上结果表明,内源性β-内啡肽和强啡肽参与可乐宁和 NE 脑室注射所引起的降压效应。     

家兔延髓最后区对心血管活动的调节

目的:探讨家兔延髓最后区(AP)对心血管活动的调节作用及机制.方法:以10%脲酯和1%氯醛糖混合静脉麻醉家兔,人工呼吸.给AP不同频率(10 Hz～80 Hz)电刺激,观察平均动脉压(MAP)和心率(HR)的变化;及损毁CVLM或RVLM后AP兴奋的心血管效应改变.结果:电刺激AP,低频(10 Hz、20 Hz)刺激使MAP下降、HR减慢;高频(60 Hz、80 Hz)刺激使MAP升高,HR减慢.损毁CVLM后刺激AP,20 Hz刺激引起的降压作用消失(P＜0.01),80 Hz刺激效应同前(P＞0.05).损毁RVLM后刺激AP,20 Hz、80 Hz刺激引起的降压、升压作用均消失(P＜0.01).结论:低频电刺激AP,引起降压和心率减慢,高频电刺激AP引起升压和心率减慢;前者可能与兴奋CVLM有关,不同电刺激引起的心血管效应均通过RVLM介导.     

急性低氧下中枢加压素对循环活动的效应

为了解中枢加压素是否参与了低氧下循环活动的维持,本实验在同步监测麻醉大鼠血压(BP)、心率(HR)、左、右心室压(LVP,RVP)及其dP/dt的条件下,观察侧脑室注射(icv.)加压素V_1-、V_2-受体拮抗剂(各4μg)及同体积人工脑脊液(ACSF)(8μl)三组不同处理大鼠在低氧下循环指标的变化。于侧脑室注射药物10min后,让大鼠吸入含氧9％的氮氧混合气体15min,然后复氧。实验中观察到三组大鼠在低氧期间,循环活动各指标均下降。但icv.V_1-受体拮抗剂一组大鼠MBP,HR,左心室压峰值(LVSP)、左心室压力变化率最大值(LV+dp/dt_(max))等循环指标下降幅度显著大于对照组(P<0.01);复氧后两组间循环指标差异逐渐消失。常氧下icv,4μg V_1-受体拮抗剂及8μl ACSF对循环活动无影响。常氧下icv.V_2-受体拮抗剂导致大鼠HR,MBP,LVSP,LV+dp/dt_(max)出现一过性升高,但在低氧、复氧期间,该组与对照组循环活动各指标间无显著性差异。上述实验结果提示低氧应激期间,中枢内源性AVP对大鼠循环功能的维持具有重要作用。该效应是通过其V_1-受体介导的,与其V_2-受体无关。在正常情况下,中枢AVP对心血管活动无紧张性影响。     

中枢苯环立啶受体介导的心血管效应

有关中枢苯环立啶（PCP）受体的心血管效应,尚未见报道,本文采用大鼠侧脑室注射（icv)、脊髓蛛网膜下腔注射（ith)和皮下注射（sc)PCP受体的激动剂或拮抗剂,观察其对血压、心率和呼吸的影响,以了解脑和脊髓PCP受体的心血管效应,结果表明,icv250nmolPCP产生强烈的降压和快速持久的心率减慢作用。ithPCP立即产生强烈的降压和心率减慢作用。并呈量效关系。ithPCP受体篁 异性拮抗剂右吗喃15nmol,可拮抗PCP（150nmol)所产生的降奔驰主和心率减慢作用,ithPCP受体特异性拮抗剂右吗喃15nmol,可拮抗PCP（150nmol)所产生的降压和心率减慢作用,ithPCP受体激动剂TCP250nmol,立即产生强烈的降压和心率减慢作用。scPCP10ng/kg则产生升压作用,对心率没有影响,上述结果表明,中枢PCP受体具有心血管抑制效应。     

蓝斑核在侧脑室注射P物质引起的升压反应中的作用

本实验在体重为280～350g乌拉坦麻醉的健康大鼠上进行,观察侧脑室注射(icv.)P物质(SP)15μg的升压反应、电损毁双侧蓝斑核(LC)后对icv.SP升压反应的影响和icv.SP对LC神经元自发放电的影响及其与血压的关系。结果表明,icv.SP可使大鼠血压明显升高(P<0.001):电损毁双侧LC对大鼠正常血压无影响,但可使icv.SP的升压反应明显减弱(P<0.001):icv.SP可使大部分有反应的LC神经元放电频率增加(P<0.001),同时血压升高,二者有平行关系。上述结果提示:LC在icv.SP引起的升压反应中具有重要作用,icv.SP的升压反应可能主要通过LC下行活动而实现。     

脑室注射组胺抑制大鼠胃酸分泌的外周机制

本文分析了第三脑室注射组胺（HA）抑制胃酸分泌效应的外周过程。雄性SD大鼠,摘除双侧肾上腺,用37℃的生理盐水通过恒流泵进行连续胃灌流。用注射器泵静脉每小时给药,观察其对五肽促胃液素（10μg/kg,iv）诱导的胃酸分泌的影响。结果如下：（1）切除双侧膈下迷走神经可阻断HA（1μg,icv）的中枢抑酸效应;（2）预先静脉注射硫酸阿托品［0.05mg／（kg·100min）］可阻断HA的中枢抑酸效应;（3）预先静脉注射生长抑素拮抗剂[2～4μg/（kg·100min）],可剂量依赖性地拮抗HA的中枢抑酸效应。结果提示：HA的中枢抑酸效应由迷走神经传出,可能通过乙酰胆碱M受体及引起生长抑素释放实现。     

安定降低家兔血压和减少刺激下丘脑诱发室性期前收缩的机制分析

家兔62只,用乌拉坦(700mg/kg)和氯醛醣(35mg/kg)静脉麻醉,三碘季铵酚制动,在人工呼吸下进行实验。用电刺激下丘脑近中线区的方法诱发室性期前收缩(HVE)。静脉注射安定(0.5mg/kg)可降低基础血压(BP),减弱刺激下丘脑引起升压反应(指收缩压峰值SBP_(max))和减少HVE。在双侧延髓腹外侧头端区(rVLM)微量注射氟安定(200μg溶于0.5μl中),γ-氨基丁酸(GABA)(6μg溶于0.5μl中)均能降低BP、SBP_(max)和减少HVE,若微量注射印防己毒素(7.5μg溶于0.5μl中)则可使BP上升并增多HVE。而于双侧延髓腹外侧尾端区(cVLM)微量注射同样剂量氟安定、GABA则无上述反应。安定降低BP、SBP_(max)和减少HVE的作用可被双侧rVLM区微量注射GABA受体拮抗剂荷包牡丹碱(3μg溶于0.5μl中)或印防己毒素所消除,但在双侧rVLM区微量注射甘氨酸受体拮抗剂士的宁(1μg溶于0.5μl中)、阿片受体拮抗剂纳洛酮(0.5μg溶于0.5μl中)、胆碱能阻断药阿托品(0.25μg溶于0.5μl中)、东莨菪碱(1.5μg溶于0.5μl中)后仍然存在。 上述结果提示,在双侧rVLM应用GABA受体拮抗剂可消除安定降低BP、SBP_(max)和减少HVE的作用,安定降低BP、SBP_(max)和减少HVE的作用可能通过GABA这一中间环节,而胆碱能受体、阿片受体、甘氨酸受体可能不起重要作用。     

延髓头端腹外侧区血管升压素能机制在应激性高血粘度中的作用

观察延髓头端腹外侧区（ｒＶＬＭ）微量注射血管升压素（ＡＶＰ）能否影响正常大鼠的血压和血粘度,并分析ｒＶＬＭ内ＡＶＰ能机制在清醒大鼠经悬吊加束缚引起应激性升压反应和高血粘度中的影响。结果如下：⑴正常大鼠双侧ｒＶＬＭ微量注射ＡＶＰ（每侧０．５μｇ／０．５μｌ）,可引起血压和血粘度升高;此作用可被事先在同一位置微量注射ＡＶＰ－Ｖ１受体拮抗剂ｄ（ＣＨ２）５「Ｔｙｒ（Ｍｅ）＾２」ＡＶＰ（每侧０．１μｇ／０．     

Opposite effects of intraventricular and intracisternal administration of vasopressin on blood pressure in rats

Lysine-8-vasopressin (LVP) was injected into the lateral ventricle (ICV) or into the cisterna magna (c.m.) of ether-anesthetized rats. ICV injection of LVP decreased the blood pressure (BP), whereas c.m. administration increased it. The opposite effects of ICV versus c.m. administration of the peptide might be related to differences in brainstem versus limbic-midbrain structures in the regulation of blood pressure, and suggest that both mechanisms can be influenced by vasopressin.     

Potentiation of the carotid artery occlusion reflex by a cholinergic system in the posterior hypothalamic nucleus

Bilateral occlusion of the common carotid arteries of urethane-anesthetized rats evoked a pressor response of 14 ± 1 mm Hg. Injection into the lateral cerebral ventricle of neostigmine (0.2–1.0 μg) or physostigmine (10–15 μg) caused a dose-dependent increase in basal blood pressure and in the magnitude of the carotid artery occlusion (CAO) pressor reflex. Neostigmine (1 μg) and physostigmine (15 μg) caused nearly maximal and approximately equal degrees of cholinesterase inhibition in several brain regions. The recovery of the cardiovascular parameters and of brain cholinesterase activity was significantly faster following physostigmine compared to neostigmine. Prior intracerebroventricular injection of atropine (0.3 μg) or hemicholinium-3 (20 μg) prevented the increases in basal pressure and the CAO pressor response. Potentiation of the CAO reflex also followed injection of physostigmine or neostigmine into the posterior hypothalamic nucleus and of injection of physostigmine intravenously. Injection of atropine bilaterally into the posterior hypothalamic nucleus prior to intravenous injection of physostigmine prevented the potentiation of the CAO reflex but not the increase in basal blood pressure. These results indicate that acetylcholine in the posterior hypothalamic nucleus serves as a neurotransmitter in a pathway which can potentiate the pressor response to carotid artery occlusion and thus modulate baroreceptor reflexes.     

延髓腹外侧头端区在第四脑室注射 P物质所致升压中的作用

实验用乌拉坦麻醉、肌内麻痹、人工呼吸的家兔。将Ｐ物质（ＳＰ,０．８ｎｇ／ｋｇ溶于１０μｌ人工脑脊液中）注入第四脑室引起肺动脉压（ＰＡＰ）升高或降低,但对坟反应为主。与此同时,颈劝脉压（ＣＡＰ）上升,心率（ＨＲ）减慢;而在第四及室内注入同容积的人工脑脊液对ＰＡＰ,ＣＡＰ和ＨＲ无明显影响。若在ｉｖｔＳＰ之前,预先向双侧延髓腹外侧头端区微量注射ＳＰ受体拮抗剂－ＳＰ（５＝１０ｎｇ溶于０．５μｌ人工脑脊液中     

家兔Bezold—Jarisch反射的血流动力学效应

在40只麻醉兔,观察经冠脉内注射尼古丁诱发Bezold-Jarisch反射时的血流动力学变化。反射效应表现为心率减慢、动脉血压和左心室收缩压降低以及左心室内压微分值减小。切断两侧窦神经和减压神经后,上述效应增强;两侧迷走神经切断后,多数动物反射效应消失。 冠脉内注射尼古丁后,心输出量和总外周阻力均下降。人工起搏心脏以防止心率减慢时,对上述效应无明显影响。动物阿托品化并切除两侧星状神经节后,心率减慢基本消失,但动脉血压降低的程度并无明显变化。结果提示,Bezold-Jarisch反射时所表现的动脉血压降低,可归因于心输出量减少和总外周阻力降低,而以后者为主。     

心房钠尿肽的中枢性心血管和肾效应

在麻醉大鼠观察了颈动脉、脊髓蛛网膜下腔和侧脑室内注射心房钠尿肽(Atrial natri-uretic peptide,ANP)后,血压,心率或/和尿量、尿钠和尿钾的变化,并观察了 ANP 对血管紧张素Ⅱ(AGⅡ)中枢效应的影响。结果如下:(1)在大鼠头部交叉循环条件下,经受血鼠颈总动脉内注射α-人心房钠尿多肽(α-human atrial natriurctic polypeptide,α-hANP)(15μg/kg)后,受血鼠平均动脉压(MAP)无改变,而供血鼠的 MAP 降低,⊿MAP为-2.4±0.84kPa(-18±6.3mmHg,P<0.05),(2)脊髓蛛网膜下腔注射心房肽,Ⅱ(AtriopeptinⅡ,APⅡ)(5μg/kg)对血压、心率和尿量无明显影响;(3)侧脑室注射 APⅡ(20μg/kg)后血压和心率无显著改变,尿量仅在注射后第30至50min 时显著增加,而尿钠无改变;(4)侧脑室注射 AGⅡ(1μg/kg),血压升高,⊿MAP 为1.3±0.17kPa(10±1.3mmHg,n=10,P<0.001)。注射1h 后,尿量增加106%(P<0.01),尿钠增加642%(P<0.01);(5)事先侧脑室注射 APⅡ(20μg/kg),2min 后再注入 AGⅡ(1μg/kg),AGⅡ的中枢升压效应不受影响,⊿MAP为1.5±0.25kPa(11±1.9mmHg,n=7,P<0.01),而尿量和尿钠的增值明显减小。以上结果表明,ANP 难于透过血脑脑脊血屏障,可能与其分子量较大有关。在静脉注射 ANP 所致降压效应中,似无中枢机制的参与。ANP 对 AGⅡ     

Central and peripheral mechanisms underlying gastric distention inhibitory reflex responses in hypercapnic-acidotic rats

We have observed that in chloralose-anesthetized animals, gastric distension (GD) typically increases blood pressure (BP) under normoxic normocapnic conditions. However, we recently noted repeatable decreases in BP and heart rate (HR) in hypercapnic-acidotic rats in response to GD. The neural pathways, central processing, and autonomic effector mechanisms involved in this cardiovascular reflex response are unknown. We hypothesized that GD-induced decrease in BP and HR reflex responses are mediated during both withdrawal of sympathetic tone and increased parasympathetic activity, involving the rostral (rVLM) and caudal ventrolateral medulla (cVLM) and the nucleus ambiguus (NA). Rats anesthetized with ketamine and xylazine or α-chloralose were ventilated and monitored for HR and BP changes. The extent of cardiovascular inhibition was related to the extent of hypercapnia and acidosis. Repeated GD with both anesthetics induced consistent falls in BP and HR. The hemodynamic inhibitory response was reduced after blockade of the celiac ganglia or the intraabdominal vagal nerves with lidocaine, suggesting that the decreased BP and HR responses were mediated by both sympathetic and parasympathetic afferents. Blockade of the NA decreased the bradycardia response. Microinjection of kainic acid into the cVLM reduced the inhibitory BP response, whereas depolarization blockade of the rVLM decreased both BP and HR inhibitory responses. Blockade of GABA(A) receptors in the rVLM also reduced the BP and HR reflex responses. Atropine methyl bromide completely blocked the reflex bradycardia, and atenolol blocked the negative chronotropic response. Finally, α(1)-adrenergic blockade with prazosin reversed the depressor. Thus, in the setting of hypercapnic-acidosis, a sympathoinhibitory cardiovascular response is mediated, in part, by splanchnic nerves and is processed through the rVLM and cVLM. Additionally, a vagal excitatory reflex, which involves the NA, facilitates the GD-induced decreases in BP and HR responses. Efferent chronotropic responses involve both increased parasympathetic and reduced sympathetic activity, whereas the decrease in BP is mediated by reduced α-adrenergic tone.     

刺激蓝斑对心肌收缩力及肾交感神经放电的影响

在64只麻醉及人工呼吸的猫,观察到电刺激蓝斑(LC)能引起血压升高、心率加快,左心室收缩压升高,左心室内压最大变化率增加及肾交感神经放电(RNA)显著地增加。去缓冲神经对电刺激 LC 所引起的上述指标的增加幅度无明显影响,但可明显延长血压反应升高相以及血压恢复期的时间。LC 内微量注射谷氨酸钠可使血压下降,心率减慢,左室收缩压和左室内压最大变化率亦降低。LC 内注射海人酸,也能引起减压反应。而注射海人酸3h 后,使LC 神经元发生变性或去极化阻断时,再电刺激 LC 仍能引起明显的升压反应。以上结果表明,电刺激 LC 可使血压升高、心肌收缩力及肾交感神经放电增加,而 LC 内微量注射胞体兴奋剂则可降低血压、心率及心肌收缩力,说明电刺激 LC 引起的加压反应可能主要是兴奋了过路纤维所致,而 LC 本身神经元的兴奋引起的是减压反应。     

Sympathetic hyperreactivity to air-jet stress in the chromosome 1 blood pressure quantitative trait locus congenic rats

A chromosome 1 blood pressure quantitative trait locus (QTL) was introgressed from the stroke-prone spontaneously hypertensive rats (SHRSP) to Wistar-Kyoto (WKY) rats. This congenic strain (WKYpch1.0) showed an exaggerated pressor response to both restraint and cold stress. In this study, we evaluated cardiovascular and sympathetic response to an air-jet stress and also examined the role of the brain renin-angiotensin system (RAS) in the stress response of WKYpch1.0. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to air-jet stress in WKYpch1.0, WKY, and SHRSP. We also examined effects of intracerebroventricular administration of candesartan, an ANG II type 1 receptor blocker, on MAP and HR responses to air-jet stress. Baseline MAP in the WKYpch1.0 and WKY rats were comparable, while it was lower than that in SHRSP rats. Baseline HR did not differ among the strains. In WKYpch1.0, air-jet stress caused greater increase in MAP and RSNA than in WKY. The increase in RSNA was as large as that in SHRSP, whereas the increase in MAP was smaller than in SHRSP. Intracerebroventricular injection of a nondepressor dose of candesartan inhibited the stress-induced pressor response to a greater extent in WKYpch1.0 than in WKY. Intravenous injection of phenylephrine caused a presser effect comparable between WKYpch1.0 and WKY. These results suggest that the chromosome 1 blood pressure QTL congenic rat has a sympathetic hyperreactivity to an air-jet stress, which causes exaggerated pressor responses. The exaggerated response is at least partly mediated by the brain RAS.