大鼠蓝斑核对血压和迷走加压反应的影响

我们观察电刺激大鼠蓝斑核对血压和迷走—加压反应的影响,其结果简述如下:一、电刺激大鼠单侧蓝斑(17只)及双侧蓝斑(27只)均引起明显的加压反应,后者更为显著。二、同时电刺激蓝斑核与迷走神经向中端引起极明显的加压反应。三、损毁垂体及切除双侧肾上腺届,蓝斑加压反应明显减弱。四、烧毁双侧蓝斑核,迷走—加压反应消失。据此我们认为迷走一加压反应可能包含蓝斑核所释放的去甲肾上腺素的作用。     

AT1受体在脑胆碱能刺激引起的蓝斑TH免疫反应活性变化中的作用

目的：探讨大鼠侧脑室注射胆碱能激动剂氨甲酰胆碱（carbachol,CBC）后蓝斑儿茶酚胺能神经元活性和血管紧张素能AT1受体表达的变化以及阻断ATl受体对上述变化的影响。方法：选用SD雄性大鼠,利用免疫组织化学方法,观察侧脑室注射氨甲酰胆碱（0．5μg）和／或losartan（20μg）后40min,蓝斑的酪氨酸羟化酶（tyrosine hydroxylase,TH）及AT1受体免疫反应活性的变化。结果：侧脑室注射氨甲酰胆碱（0．5pg）后40min,蓝斑的TH及ATl受体免疫反应阳性神经元数目明显增多（P〈0．05）,免疫染色强度明显增强（P〈0．05）。losartan预处理后蓝斑的TH免疫反应活性和AT1受体表达明显下降（P〈0．05）。结论：侧脑室注射胆碱能激动剂氨甲酰胆碱对蓝斑儿茶酚胺能神经元具有兴奋作用,AT1受体表达增强;阻断脑血管紧张素能AT1受体可下调氨甲酰胆碱在蓝斑诱导的上述变化。     

猫中缝大核与蓝斑复合核区:两个不同的调制血管反射活动的结构

在无麻醉的麻痹猫,电刺激内脏大神经或腓总神经、阻断颈总动脉血流所引起的加压反射和皮肤电阻下降,在损毁双侧蓝斑复合核区后均明显减弱,而在损毁延髓中缝大核区后则大为增强。这两种效应在去大脑动物仍可出现。若先损毁中缝大核,则损毁蓝斑复合核的效应难以出现。上述脑损毁本身均不影响血压水平。以弱电流刺激蓝斑复合核通常强化这些反射,而刺激中缝大核有时可压抑它们。在胸8水平切断双侧背外侧索的背部,不影响窦加压反射,但有时增强内脏大神经加压反射;在颈2水平切断则使这两种加压反射不同程度地增强。本结果提示:中缝大核对主管血管反射活动的延髓-脊髓回路起着紧张性抑制作用,而蓝斑复同核则起着兴奋性作用。     

眶额叶微量注射谷氨酸和γ-氨基丁酸对胃运动的影响及其机制探讨

目的:研究眶额叶(OFC)的谷氨酸(Glu)和γ-氨基丁酸(GABA)含量变化对胃运动的影响及其调节神经机制。方法:实验采用了大鼠眶额叶微量注射给药,结合核团损毁的方法,以记录胃内压,统计胃收缩幅度作为胃运动变化的指标。结果:①OFC注射Glu可显著降低胃收缩幅度,损毁杏仁核后可反转该效应,胃收缩幅度显著增强;损毁蓝斑核后,Glu的作用无显著性变化。②OFC注射GABA可显著增强胃的收缩幅度,损毁蓝斑核后消除该效应;损毁杏仁核后,胃收缩幅度进一步增强。结论:外源性增加OFC区Glu含量导致的抑胃效应可能是通过增强了杏仁核的经常性抑胃作用而引起的;而增加OFC区GABA的含量引起的胃运动增强与蓝斑核密切相关。     

损毁和刺激蓝斑复合核对内脏躯体反射抑制效应的影响

以电刺激腓总神经对内脏躯体反射活动的抑制效应为指标,观察蓝斑复合核在此抑制效应中所起的作用,并对其作用途径进行初步分析。(1)损毁双侧蓝斑复合核大部分后,绝大部分动物上述的抑制效应有不同程度增强;(2)去大脑,损毁中缝背核或蓝斑复合核后方的相应区域对此抑制效应没有影响,此后再毁蓝斑复合核,仍可出现上述抑制效应增强的现象;若损毁延脑中缝大核区,则此增强现象不再出现。(3)以弱电流刺激蓝斑复合核中的某些点,本身并不引起任何效应,但可部分削弱腓总神经的抑制效应。据此推测,蓝斑复合核中某些成分的活动对针刺的下行性抑制效应起着紧张性的压抑作用,这一作用很可能主要施加于延脑中缝大核的痛觉调制系统或通过它来实现。     

大鼠蓝斑组胺受体在应激导致颈动脉窦反射重调定中的作用

目的：揭示蓝斑（LC）的H1和H2受体在足底电击应激对颈动脉窦反射（CBR）重调定中的作用。方法：足底电击应激1周的SD大鼠,麻醉后孤离双侧颈动脉窦区,将不同窦内压（ISP）与其对应的平均动脉压（MAP）值进行Logistic五参数曲线拟合,求得ISP-MAP、ISP-增益（Gain）关系曲线及反射特征参数,观察Lc微量注射选择性H1或H2,受体拮抗剂氯苯吡胺（CHL）或西咪替丁（CIM）对应激状态下CBR的影响。结果：应激导致ISP-MAP关系曲线显著全面上移（P〈0.05）,ISP-Gain关系曲线中部明显下移（P〈0.05）,反射参数中闪压、饱和压、调定点和最大增益时的ISP值增大（P〈0.05）,而MAP反射变动范围及反射最大增益减小（P〈0.05）;LC内注射CHL（0.5μg/μl）或CIM（1.5μg/μl）20min内均可明显减弱应激对CBR的上述改变（P〈0.05）,CIM的减弱效应不如CHL的显著（P〈0.05）;LC注射上述相同剂量的CHL或CIM对非应激大鼠的CBR无明显影响（P〉0.05）;LC内注射CHL或CIM均不能使应激的CBR水平完全恢复到相应的非应激对照水平。结论：应激引起CBR重调定,反射敏感性下降;部分机制可能是激活中枢纽胺能系统,LC的H1和H2受体尤为H1受体在应激对CBR的重调定机制中发挥重要作用,下丘脑-LC的组胺能通路可能是应激所致CBR重调定的下行通路之一;除此之外,应激作用中尚有其他因素的参与。     

痛血康胶囊对早孕大鼠不完全流产模型的治疗作用

目的：探讨痛血康胶囊治疗早孕SD大鼠不完全流产模型产后出血的疗效及作用机制。方法：1）受孕7 d予米非司酮和米索前列醇,造成早孕不完全流产模型,痛血康治疗7 d观察并记录SD大鼠离体子宫平滑肌活动情况及病理组织学改变。2）用小鼠尾尖取血法,观察痛血康对小鼠出凝血时间的影响。3）用小鼠耳廓肿胀和SD大鼠棉球肉芽肿两个模型,观察痛血康的抗炎作用。4）用皮下注射肾上腺素加冰水刺激所致SD大鼠血瘀模型,观察痛血康的活血化瘀作用。结果：痛血康能增强早孕不完全流产SD大鼠子宫平滑肌收缩强度,促进残存的胚囊组织排出;能降低血瘀模型SD大鼠全血和血浆黏度,缩短小鼠出凝血时间;对二甲苯所致小鼠耳廓肿胀和SD大鼠棉球肉芽肿有明显抑制作用。结论：痛血康在早孕SD大鼠中具有治疗产后出血的作用,可能与增强流产SD大鼠的子宫收缩强度、促进残留在宫腔的绒毛或蜕膜组织排出、缩短出凝血时间、抑制炎症等有关。     

损毁缰对应激性高血压形成的影响

目的和方法：运用核团损毁和微量注射的方法观察损毁缰核（Ｈｂ）对应激性高血压（ＳＩＨ）形成进程的影响及ＳＩＨ大鼠Ｈｂ内神经元对Ｌ－谷氨酸反应性的变化。结果：（１）损毁双侧Ｈｂ延缓了ＳＩＨ的形成进程;（２）在ＳＩＨ大鼠内侧Ｈｂ（ＭＨｂ）微量注射不同浓度的ＣＩｕ,血压明显升高;呈浓度依赖性,升高值与正常大鼠ＭＨｂ注入等量Ｇｌｕ引起的升高值相比,有显著性差异;（３）在ＳＩＨ大鼠外侧Ｈｂ（ＬＨｂ）注入不同浓     

基底外侧杏仁核对睡眠-觉醒的调节作用

采用多道睡眠描记方法,观察了基底外侧杏仁核在睡眠－觉醒调节中的作用。结果发现,电损毁双侧ＢＬＮ引起慢波睡眠和快波睡眠增加,觉醒减少;在双侧ＢＬＮ内注射选择性损毁神经元胸体剂量的红藻氨酸引起双相效应,注射ＫＡ后第１天出现失眠,自第３天开始,ＳＷＳ增多,Ｗ减少,但ＰＳ无显著变化。     

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。     

Cardiovascular effects of histamine administered intracerebroventricularly in critical haemorrhagic hypotension in rats.

The study was designed to determine the cardiovascular effects of histamine administered intracerebroventricularly (icv) in a rat model of volume-controlled haemorrhagic shock. The withdrawal of approximately 50% of total blood volume resulted in the death of all control saline icv treated animals within 30 min. Icv injection of histamine produced a prompt dose-dependent (0.1-100 nmol) and long-lasting (10-100 nmol) increase in mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR), with a 100% survival of 2h after treatment (100 nmol). The increase in MAP and HR after histamine administration in bled rats in comparison to the normovolaemic animals was 2.7-3.3- and 1.3-3.6-fold higher, respectively. Pretreatment with chlorpheniramine (50 nmol icv), H1 receptor antagonist, inhibited the increase in MAP, PP, HR and survival rate produced by histamine, while chlorpheniramine given alone had no effect. Neither ranitidine (50 nmol icv), H2 histamine receptor antagonist, nor thioperamide (50 nmol icv), H3 receptor blocker, influenced the histamine action, however, when given alone, both evoked the pressor effect with elongation of survival time. It can be concluded that histamine administered icv reverses the haemorrhagic shock conditions, and histamine H1 receptors are involved.     

Histamine in stress ulcer prophylaxis in rats.

BACKGROUND: Gastrin and its analogues increase the gastric acid secretion, but also enhance mucosal defense mechanisms. On the other hand, increased formation of histamine leading to an increase in gastric acid secretion is accompanied with gastroprotection and acceleration of gastric ulcer healing. AIM: Of this study was to examine the effect of histamine on stress induced gastric ulcers in rats. METHODS: Male Wistar rats were exposed to water immersion and restrain stress (WRS) for 3.5 h at 23 degrees C. Before WRS rats were pretreated with saline, histamine, ranitidine or omeprazole. RESULTS: WRS produces gastric lesions which were strongly reduced by ranitidine or omeprazole. Also treatment with histamine markedly reduced ulcer area evoked by WRS. Addition of histamine to ranitidine or omeprazole caused an additional reduction in ulcer area. Gastroprotective effect of histamine was accompanied with the increase in gastric blood flow (GBF). Administration of omeprazole or ranitidine alone was without significant effect on GBF. Histamine caused an slight decrease in gastric luminal pH, whereas ranitidine or omeprazole significantly increased gastric luminal pH. Plasma interleukin-1beta was significantly reduced after administration of omeprazole, ranitidine, or histamine, however, the effect of histamine was less pronounced. DNA synthesis was increased after administration of omeprazole, ranitidine or histamine when compared with WRS alone. Administration of histamine in combination with ranitidine or omeprazole caused an additional increase in DNA synthesis. CONCLUSIONS: Histamine exhibits protective effect and increases gastroprotective effect of ranitidine and omeprazole against stress-induced gastric lesions. This effect of histamine seems to be independent on gastric acid secretion but related to the increase in gastric blood flow and the reduction in activation of cytokine cascade.     

Histamine H2 receptor: involvement in gastric ulceration.

The involvement of the H1 and H2 receptors for histamine in the pathogenesis of gastric ulcers was investigated in rats. Metiamide, an H2 receptor antagonist, reliably reduced ulceration produced by stress alone or by a combination of stress and aspirin. In contrast, pyrilamine, which blocks only the H1 receptor, was without effect under these same conditions. The results support the hypothesis that histamine mediates both stress and stress plus aspirin induced ulceration by a mechanism involving the H2 receptor.     

Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence

The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle parts of the urethra increased, the response in the proximal urethra was almost negligible when the bladder response was subtracted from the urethral response or when the abdomen was opened. In contrast, the response in the middle urethra during sneezing was still observed after subtracting the bladder response or after opening the abdomen. These responses in the middle urethra during sneezing were significantly reduced approximately 80% by bilateral transection of the pudendal nerves and the nerves to the iliococcygeous and pubococcygeous muscles but not by transection of the visceral branches of the pelvic nerves and hypogastric nerves. The sneeze leak point pressure was also measured to investigate the role of active urethral closure mechanisms in maintaining total urethral resistance against sneeze-induced urinary incontinence. In sham-operated rats, no urinary leakage was observed during sneeze, which produced an increase of intravesical pressure up to 37 +/- 2.2 cmH2O. However, in nerve-transected rats urinary leakage was observed when the intravesical pressure during sneezing exceeded 16.3 +/- 2.1 cmH2O. These results indicate that during sneezing, pressure increases elicited by reflex contractions of external urethral sphincter and pelvic floor muscles occur in the middle portion of the urethra. These reflexes in addition to passive transmission of increased abdominal pressure significantly contribute to urinary continence mechanisms under a sneeze-induced stress condition.     

Effect of vaginal distension on blood flow and hypoxia of urogenital organs of the female rat.

Vaginal delivery of children causes traumatic injury to tissues of the pelvic floor and is correlated with stress urinary incontinence; however, the exact mechanism of organ and tissue injury leading to incontinence development is unknown. The purpose of this project was to test the hypothesis that vaginal distension results in decreased blood flow to, and hypoxia of, the urogenital organs responsible for continence, which would suggest an ischemic and/or reperfusion mechanism of injury. Thirteen female rats underwent vaginal distension for 1 h. Thirteen age-matched rats were sham-distended controls. Blood flow to the bladder, urethra, and vagina were determined using a microsphere technique. Hypoxia of these organs was determined by immunohistochemistry. Blood flow to all three organs was significantly decreased just before release of vaginal distension. Bladder blood flow decreased further immediately after release of vaginal distension and continued to be significantly decreased 15 min after the release. Blood flow to both the urethra and vagina tripled immediately after release, inducing a rapid return to normal values. Vaginal distension resulted in extensive smooth muscle hypoxia of the bladder, as well as extensive hypoxia of the vaginal epithelium and urethral hypoxia. Bladders from sham-distended rats demonstrated urothelial hypoxia as well as focal hypoxic areas of the detrusor muscle. We have clearly demonstrated that vaginal distension results in decreased blood flow to, and hypoxia of, the bladder, urethra, and vagina, supportive of hypoxic injury as a possible mechanism of injury leading to stress urinary incontinence.     

Age-related differences in the cardiovascular responses to haemorrhagic shock in rats.

The cardiovascular responses to haemorrhagic shock were studied in male Sprague-Dawley rats of different age groups, ranging from 6-15 weeks (body weight 250-460 g). Haemorrhagic shock was induced by bleeding (2% body weight), under urethane anaesthesia, from the cannulated femoral artery at a rate of 1 ml/min. It was found that the younger rats had significantly smaller values of left ventricular pressure and dLVP/dtmax following haemorrhage and a greater mortality rate. Older animals exhibited significantly greater falls in blood pressure and pulse rate during the bleeding procedure, and slower recovery in these parameters after the bleeding was stopped. However, these rats had a significantly higher left ventricular pressure and dLVP/dtmax following haemorrhage, and a markedly lower mortality rate. The findings demonstrate the existence of age-related cardiovascular responses to haemorrhagic shock in rats.     

Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury

Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.     

Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats

In rodents, maternal pup interactions play an important role in programming the stress responsiveness of the adult organism. The aims of this study were 1) to determine the effect of different neonatal rearing conditions on acute and delayed stress-induced visceral sensitivity as well as on other measures of stress sensitivity of the adult animal; and 2) to determine the role of corticotropin-releasing factor receptor (CRF-R) subtype 1 (CRF(1)R) in mediating visceral hypersensitivity. Three groups of male Long-Evans rat pups were used: separation from their dam for 180 min daily from postnatal days 2-14 (MS180), daily separation (handling) for 15 min (H), or no handling. The visceromotor responses (VMR) to colorectal distension, stress-induced colonic motility, and anxiety-like behavior were assessed in the adult rats. The VMR was assessed at baseline, immediately after a 1-h water avoidance (WA) stress, and 24 h poststress. Astressin B, a nonselective CRF-R antagonist, or CP-154,526, a selective CRF(1)R antagonist, was administered before the stressor and/or before the 24-h measurement. MS rats developed acute and delayed stress-induced visceral hyperalgesia. In contrast, H rats showed hypoalgesia immediately after WA and no change in VMR on day 2. MS rats with visceral hyperalgesia also exhibited enhanced stress-induced colonic motility and increased anxiety-like behavior. In MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR. Rearing conditions have a significant effect on adult stress responsiveness including immediate and delayed visceral pain responses to an acute stressor. Both acute and delayed stress-induced visceral hypersensitivity in MS rats are mediated by the CRF/CRF(1)R system.     

Effect of the NK-1 receptor antagonist GR 82,334 on reflexly-induced bladder contractions.

The effect of intrathecal administration of the novel tachykinin NK-1 receptor antagonist GR 82,334 has been tested in three reflexes which excite urinary bladder motility. GR 82,334 at 1 but not at 0.1 nmol/rat blocked the chemonociceptive micturition reflex induced by the topical application of capsaicin (4 micrograms/50 microliters) onto the urinary bladder. At the same dose proven effective in the chemonociceptive reflex, GR 82,334 did not affect either micturition reflex induced by bladder filling or the urinary bladder contraction induced by perineal pinching. These results suggest that, in urethane-anesthetized rats, specific stimuli applied in the periphery activate NK-1 receptors at spinal cord level facilitating urinary bladder reflex contractions.