原发性高血压大鼠降压过程中心钠素和加压素变化的研究

本文研究心得安、异搏定引起原发性高血压大鼠(SHR)降压过程中血浆心钠素(A)和精氨酸加压素(AVP)含量,以及心房、肾、胰腺、脾、脑组织中ANF含量。动物随机分为3组:对照组、心得安组和异搏定组。结果血浆ANF件别为26.89±2.95,20.80±6.77(P<0.01),13.76±4.69(P<0.01)ng/ml,实验组均显著降低,血浆AVP对照组为13.65±0.92,心得安组为2364±15.29(P<0.01)显著升高,异搏定组为12.58±1.85(P<0.05)pg/ml显著降低。实验组脑干ANF明显降低;左右心房、脑半球ANF明显升高。提示:SHR血浆及所测组织中均有ANF或ANF样免疫活性物质存在,且在降压过程中,ANF合成与释放均有明显改变并与AVP相互制约共同发挥调节作用。     

α—MSH对家兔ET性发热反应及脑腹中隔区AVP含量的影响

目的：研究脑腹中隔区精氨酸加压素（ＡＶＰ）在α－黑素细胞刺激素（αＭＳＨ）解热机制中的作用。方法：建立家兔ＥＴ性发热模型，观察侧脑室注射α－ＭＳＨ对家兔ＥＴ性发热反应及脑腹中隔区ＡＶＰ含量的影响。结果：（１）静脉注射ＥＴ（０３μｇ／ｋｇ）引起家兔明显的发热反应（Ｐ＜０００１），并增加脑腹中隔ＡＶＰ含量（Ｐ＜００５）；（２）静脉注射ＥＴ（０３μｇ／ｋｇ）３０ｍｉｎ后，侧脑室注射α－ＭＳＨ（２００ｎｇ／只），能明显抑制家兔发热反应，同时脑腹中隔区ＡＶＰ含量进一步显著增高（Ｐ＜０００１）；（３）侧脑室注射α－ＭＳＨ（２００ｎｇ／只）并不影响家兔正常体温，但增加脑腹中隔区ＡＶＰ含量（Ｐ＜００５）。结论：α－ＭＳＨ的解热作用可能部分是通过腹中隔ＡＶＰ增多来实现的，αＭＳＨ可能是引起发热时脑腹中隔区ＡＶＰ含量增加的一个重要因素。     

α-MSH对EGTA性发热效应及脑腹中隔AVP含量的影响

目的和方法：观察脑腹中隔精氨酸加压素（ＡＶＰ）在α－黑素细胞刺激素（α－ＭＳＨ）解热机制中的作用；用放射免疫法测定ＡＶＰ含量。结果：ＥＧＴＡ引起明显的发热反应（Ｐ＜０．０１），同时降低脑腹中隔ＡＶＰ含量（Ｐ＜０．０５）。α－ＭＳＨ可抑制ＥＧＴＡ性发热反应（Ｐ＜０．０１），并增加脑腹中隔ＡＶＰ含量（Ｐ＜０．０５）；而对正常家兔体温及脑腹中隔ＡＶＰ含量无影响（Ｐ＞０．０５）。结论：α－ＭＳＨ对ＥＧＴＡ的解热作用可能部分是通过增加脑腹中隔ＡＶＰ的释放而实现的。在限制发热的过程中，内生解热物α－ＭＳＨ与ＡＶＰ可能具有协同作用。     

脑热清对内毒素性发热家兔下丘脑、脑脊液cAMP及腹中隔区AVP含量的影响

目的:探讨脑热清(NRQ)口服液的解热机制。方法:复制家兔内毒素(ET)性发热模型,观察NRQ对家兔体温的影响;用放射免疫法检测下丘脑和脑脊液(CSF)中cAMP及腹中隔区AVP含量的变化。结果:(1)NRQ+ET组的ΔT[(0.82±0.08)℃]、TRI₆(5.73±0.09)、下丘脑cAMP含量[(0.70±0.50)nmol/g]、CSF中cAMP含量[(56.86±1.34)nmol/L]及腹中隔区AVP含量[(11.91±3.47)ng/g],分别低于ET组的ΔT[(1.80±0.16)℃]、TRI₆(11.31±0.20)、下丘脑cAMP含量[(1.35±0.21)nmol/g]、CSF中cAMP含量[(66.69±1.82)nmol/L]、腹中隔区AVP含量[(30.80±9.59)ng/g],两者相比有显著差异(P<0.01)。(2)4组的体温变化分别与下丘脑和CSF中cAMP以及腹中隔区AVP的变化呈正相关(下丘脑:r=0.899,P<0.05;CSF:r=0.991,P<0.01;AVP:r=0.972,P<0.01)。结论:NRQ的解热机制可能是通过抑制下丘脑cAMP的生成与释放,同时通过促进腹中隔AVP释放两种途径发挥作用。     

脑热清对EP性发热家兔下丘脑、脑脊液cAMP及腹中隔区AVP含量的影响

目的 :通过复制家兔内生致热原 (EP)性发热模型 ,探讨脑热清 (NRQ)口服液的解热机制。方法 :实验分两部分进行。第 1部分观察NRQ对家兔EP性发热的解热效应。将 2 0只家兔随机分成 4组。NS组 :NS 2 4mL/kg剂量灌胃 ;NRQ组 :NRQ 2 4mL/kg灌胃 ;EP组 :EP 1 5mL/kg耳缘静脉注射 ;NRQ +EP组 :NRQ 2 4mL/kg灌胃 ,0 5h后耳缘静脉注射EP(剂量同EP组 )。实验中每 10min记温 1次 ,观察 4h ,观测指标 :最大体温上升高度 (ΔT) ,体温反应指数 (TRI)。第 2部分观察NRQ对EP性发热家兔的下丘脑和脑脊液 (CSF)中cAMP及腹中隔区精氨酸…     

中枢CRH在大鼠应激性体温升高和LPS性发热机制中的作用

目的:进一步观察中枢促肾上腺皮质激素释放激素(CRH)在大鼠应激性体温升高和脂多糖(LPS)性发热中枢机制中的作用。方法:第三脑室微量注射CRH受体拮抗剂α-helicalCRH(9-41)和LPS,测定大鼠结肠温度及脑腹中隔区精氨酸加压素(AVP)含量。结果:生理盐水对照组大鼠体温明显升高,最大升幅为(0.88±0.31)℃。第三脑室注射CRH受体拮抗剂α-helicalCRH(9-41)10min后再注射生理盐水组,90min内大鼠结肠温度未见明显波动,90min后体温开始上升,1.5h体温反应指数(TRI_1.5)明显低于生理盐水对照组,而脑腹中隔区AVP含量和TRI_3.5与对照组比较均没有明显差别。第三脑室注射300ng的LPS引起大鼠结肠温度双相性升高,其TRI_3.5明显高于生理盐水对照组。事先向第三脑室注射α-helicalCRH(9-41)(5μg)再注射LPS组,TRI_3.5明显高于LPS组,而脑腹中隔区AVP含量明显低于LPS组。结论:CRH介导应激诱导的早期体温升高。CRH可能通过诱导脑腹中隔区AVP的生成限制大鼠LPS性发热。在大鼠LPS性发热中,CRH可能是一种双相作用分子,一方面本身介导发热体温升高,另一方面又诱生发热体温负调节介质而限制发热体温的升高。     

多发性梗塞性脑痴呆大鼠脑内神经肽的变化

目的:探讨多发性梗塞性脑痴呆(MID)与脑区内生长抑素(SS)、精氨酸加压素(AVP)和P物质(SP)的相关性及临床意义。方法:建立MID大鼠模型,对该模型及假手术对照组大鼠进行记忆行为测试,并用放射免疫分析(RIA)测定脑区(额区皮质、颞区皮质、海马、丘脑和纹状体)中SS、AVP、SP的含量。结果:在10d的记忆测试中,第1d两组大鼠出错次数均无明显差别,第3d到第10d,模型组大鼠出错次数均明显高于假手术对照组(P<0.05)。模型组的额区皮质、颞区皮质、海马、丘脑和纹状体中SS、AVP相对含量均较假手术对照组有显著下降(P<0.05,P<0.01);SP含量除在丘脑区无显著性差异外(P>0.05),在其余四个脑区均有显著降低(P<0.05,P<0.01)。结论:动物学习、记忆功能障碍可能与多发性脑梗塞后SS、AVP和SP含量下降有关。     

脱甘氨酰胺精氨酸加压素引起小鼠脑内突触结构可塑性变化的定量观察

本实验对脱甘氨酰胺精氨酸加压素(DGAVP)引起的小鼠脑内Gray Ⅰ型突触界面某些结构的变化进行了定量观察。腹腔注射DGAVP(2μg/0.2ml/只),2小时后处死动物并取脑,按常规方法进行超微结构观察。在放大的透射电镜照片上用微机图像处理系统进行定量分析。结果表明:1.在DGAVP组海马CA_3区与皮层感觉运动区,突触后膜致密物质厚度都显著地大于对照组(P<0.01);2.DGAVP组海马CA_3区的突触间隙宽度比对照组显著下降(P<0.01),突触界面曲率亦显著减小(P<0.05),而皮层感觉运动区的这两个参数无变化;3.两个脑区的突触活性区长度均无显著性变化(P>0.05)。实验结果提示,DGAVP的中枢效应可能与脑内兴奋型突触界面结构的可塑性有关。     

清开灵对内毒素性发热家兔下丘脑cAMP及腹中隔区AVP含量的影响

目的:探讨清开灵(QKL)注射液的解热机制。方法:建立家兔内毒素(ET)性发热模型,观察清开灵对家兔体温的影响和用放免法检测下丘脑cAMP及腹中隔区AVP含量的变化。结果:①ET组的△T为(1.68±0.46)℃、TRI₆为29.59±10.39、下丘脑cAMP含量为(2.90±0.40)nmol/g、腹中隔区AVP含量为(47.32±3.77)ng/g,分别显著高于NS组的△T、TRI₆(-0.15±4.29)、下丘脑cAMP含量,腹中隔区AVP含量及QKL+ET组的△T、TRI₆(13.71±3.29)、下丘脑cAMP含量、腹中隔区AVP含量(P＜0.01)。②四组下丘脑cAMP含量变化与体温变化呈明显正相关(r=0.904,P＜0.01)。结论:清开灵的解热机制可能是通过抑制下丘脑cAMP生成,同时通过腹中隔AVP而发挥作用。     

脑室注射α-helical CRH对大鼠LPS性发热 及中隔区AVP含量的影响

目的和方法 :促肾上腺皮质激素释放激素 (ｃｏｒｔｉｃｏｔｒｏｐｉｎｒｅｌｅａｓｉｎｇｈｏｒｍｏｎｅ ,ＣＲＨ)是一种重要的中枢发热介质。为进一步观察ＣＲＨ在大鼠ＬＰＳ性发热中的作用 ,本研究观察了第三脑室注射ＣＲＨ受体拮抗剂α-ｈｅｌｉｃａｌＣＲＨ( 9- 41 )对ＳＤ大鼠ＬＰＳ性发热及脑中隔区精氨酸加压素 (ａｒｇｉｎｉｎｅｖａｓｏｐｒｅｓｓｉｎ ,ＡＶＰ)含量的影响。结果 :第三脑室注射 30 0ｎｇ的ＬＰＳ引起大鼠结肠温度双相性升高 ,其 3 5ｈ发热反应指数 (ｔｈｅｒｍａｌｒｅｓｐｏｎｓｅｉｎｄｅｘ ,ＴＲＩ3.5)明显高于…     

Blood pressure maintenance in awake dehydrated rats: renin, vasopressin, and sympathetic activity

The role of vasopressin, the renin system, and sympathetic activity in sustaining blood pressure in the dehydrated state was investigated in normotensive nonanesthetized male Wistar rats. After 48-h dehydration, plasma arginine vasopressin was 14.0 +/- 1.7 pg/ml and plasma norepinephrine 0.46 +/- 0.05 ng/ml. In another group of rats in which the angiotensin converting enzyme inhibitor (MK 421, 5 mg po twice daily) was administered throughout the dehydration period, blood pressure was reduced by more than 20% (P less than 0.001), and both plasma arginine vasopressin and norepinephrine were higher at 23.4 +/- 3.9 pg/ml (P less than 0.01) and 0.83 +/- 0.07 ng/ml (P less than 0.01), respectively. Taken together, in rats with or without converting enzyme blockade, there was an inverse correlation between mean blood pressure and plasma arginine vasopressin (r = 0.67, P less than 0.01) as well as plasma norepinephrine (r = 0.82, P less than 0.01) levels. The acute administration of a specific vasopressin pressor inhibitor (dPVDAVP) reduced mean blood pressure in the rats with a blocked renin system by 16.9 mmHg (P less than 0.001). In rats without converting enzyme inhibition, the induced fall was only 6.4 mmHg. These results indicate that following 48-h dehydration the renin angiotensin system interacts with the vasopressin secretory mechanism to sustain blood pressure, with renin playing a predominant role. They further suggest that, following blockade of the renin system, activation of the sympathetic nervous system probably also contributes to blood pressure maintenance.     

精氨酸加压素在内毒素热限形成中的作用

本文观察了家兔静脉注射不同剂量ＥＴ后中隔区，下丘脑组织及血浆中ＡＶＰ含量的变化。结果显示：在ＥＴ发热过程中，中隔区，下丘脑及血浆ＡＶＰ含量均显著增多（Ｐ＜０．０１）；ＥＴ发热达热限时，体温不再升高，中隔区与血浆ＡＶＰ含量也不再增多，且中隔区及血浆ＡＶＰ含量变化与体温变化呈明显正相关（ｒ＝０．９８４，０．０５＜Ｐ＜０．０１；ｒ＝０．９９４，Ｐ＜０．０１）；此时，下丘脑升高的ＡＶＰ含量开始下降（Ｐ０。     

Observations on the mechanism of salicylate-induced antipyresis

1. Fever has been produced in conscious rabbits, first, by injection of leucocyte pyrogen into the lateral cerebral ventricle and, second, by local cooling of the hypothalamus.2. Both intravenous and intraventricular salicylate produce antipyresis during an established fever due to intraventricular leucocyte pyrogen. This is incompatible with the hypothesis that salicylate acts by interfering with the passage of leucocyte pyrogen from the circulation into the hypothalamus.3. Intravenous sodium salicylate has no effect on the fever due to local cooling of the hypothalamus. This suggests that salicylates do not act on central or peripheral efferent pathways involved in thermoregulation.     

Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

Summary The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0±0.25 vs 2.4±0.2 ng AngI/ml/h;p}<0.01) and glucagon levels (40±11 vs 20±16 pg/ml;p}<0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE₂, and PGF_2alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r=0.7;p}<0.001) and urinary postaglandin E₂ and glomerular filtration (r=0.52;p}<0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.Abbreviations PAH paraaminohippuric acid - ANF atrial natriuretic factor - AVP arginine vasopressin - PRA plasma renin activity - ERPF effective renal plasma flow - GFR glomerular filtration rate - TRP tubular reabsorption of phosphate - NE norepinephrine - E epinephrine - DA dopamine - GH growth hormone     

Sodium salicylate: alternate mechanism of central antipyretic action in the rat

Infusion of sodium salicylate (50.0 or 100.0 g/l) into the ventral septal area (VSA) of the rat brain suppressed Prostaglandin-E₁-induced hyperthermia. Infusion of artificial cerebrospinal fluid (aCSF) or 10.0 g doses of salicylate did not. The suppression of intracerebroventricularly-induced (icv) Prostaglandin E₁ (PGE₁) hyperthermia was not due to a hypothermic action of salicylate since salicylate infusions given during cold exposure (10.0°C) did not lower core body temperatures. A possible interaction between salicylate and endogenous arginine vasopressin (AVP) was investigated. Infusion of both salicylate (50.0 g/l) and either AVP antiserum or AVP antagonist into the VSA resulted in PGE hyperthermias occurring at levels which were not different from control levels as opposed to enhanced hyperthermia (antiserum or antagonist alone) or suppressed hyperthermia (salicylate alone). These results are consistent with the notion that sodium salicylate infusions within the VSA enhance AVP action and thus bring about the attenuation of PGE-induced hyperthermia.     

A cytochemical bioassay for arginine vasopressin: preliminary studies

A new method of measuring vasopressin activity is described. It depends on the finding that the Na+-K+-ATPase activity, measured cytochemically, in the thick ascending limb of the loop of Henle in rat renal tissue maintained in vitro, responded to increasing concentrations of synthetic arginine vasopressin in a log-dose related fashion. The limit of sensitivity was 0.002 pg/ml (2 x 10(-15) mol/l). The dose-responses were reproducible; the inter-assay coefficient of variation was 6.4% at a vasopressin concentration of 0.02 pg/ml. Normal plasma stimulated this Na+-K+-ATPase activity, the stimulation being reduced by 98% when the plasma had been treated with an antiserum specific for vasopressin. Measured in this system, the circulating levels of plasma vasopressin, in healthy adults after 18h dehydration, was 4.0 +/- 0.3 pg/ml (mean +/- SEM; n = 4) and fell to 0.6 +/- 0.1 pg/ml following a water load. Absolute plasma vasopressin values obtained by the cytochemical bioassay were comparable to those measured by radioimmunoassay (r = +0.97, p less than 0.001).     

Interaction of somatostatin with PTH and AVP: renal effects.

Six conscious intact dogs were studied to evaluate the interactions of somatostatin (SRIF) with exogenous antidiuretic hormone arginine vasopressin (AVP). SRIF administration caused a significant increase in free water clearance compared to a vehicle-treated group: -0.91 (+/- 0.41 SD) ml/min to 0.21 (+/- 0.32 SD) ml/min in the experimental group (P less than 0.01) versus 0.21 (+/- 0.81 SD) ml/min to -0.21 (+/- 0.68 SD) ml/min in the control (P greater than 0.5). Six conscious, thyroparathyroidectomized dogs were studied to test the interaction of SRIF and parathyroid extract (PTE). There were no significant changes in the phosphaturic and hypocalciuric effects of PTE with SRIF administration. We conclude that acute systemic SRIF administration interferes with the antidiuretic action of AVP, probably at the renal-tubular level, but does not antagonize the renal actions of PTE.     

Factors influencing the sensitivity of the rat to vasopressin

1. Indirect evidence suggests that the concentration of arginine vasopressin in the plasma of normally hydrated man is about 1 mu-u./ml., but this is usually considered to be below the limit of sensitivity of the standard assay preparation, the water-loaded Wistar rat under ethanol anaesthesia.2. It was found that there was a surprising variation in sensitivity to vasopressin between batches of Wistar rats, and that other varieties of rat (including those with diabetes insipidus) were no more sensitive.3. Three modifications of the standard assay procedure produced an increase in sensitivity:(a) using Wistar rats weighing 100-150 g, rather than larger animals;(b) commencing the assay shortly after surgery, i.e. as soon as the urine flow reached 25 mul./min;(c) infusing vasopressin intravenously (0.5-3 mu-u./min). By using modification (a) with either (b) or (c) it was possible to detect as little as 0.5 mu-u.4. With these modifications antidiuretic activity equivalent to 0.5-2.0 mu-u./ml. of arginine vasopressin was measured in nine samples of plasma from a normally hydrated subject.5. It is suggested that the frequent reports of enhanced sensitivity may have been due to the fortuitous use of a particularly sensitive batch of rats, or to a high endogenous secretion of vasopressin due to operative trauma.     

Properties of glutaminase of crayfish CNS: implications for axon-glia signaling

Previous studies have shown that arginine vasopressin is an important neuropeptide that can modulate the reflex control of blood pressure and heart rate. The nucleus ambiguus, where cardiac parasympathetic neurons are located, receives dense arginine vasopressin projections. However the mechanisms by which arginine vasopressin alters cardiac parasympathetic activity are unknown. We tested the hypothesis that arginine vasopressin can alter the activity of cardiac parasympathetic neurons by altering the spontaneous GABAergic input to these neurons. Experiments were conducted using whole cell patch clamp recordings of cardiac parasympathetic neurons in an in vitro slice preparation in rats. The results of this study demonstrate that arginine vasopressin increases the frequency and amplitude of GABAergic inhibitory post-synaptic currents in cardiac parasympathetic neurons. Arginine vasopressin did not alter the GABAergic currents evoked by exogenous application of GABA. Similarly, in the presence of tetrodotoxin, arginine vasopressin did not alter the frequency, amplitude or decay time of GABAergic miniature synaptic events evoked by high osmolarity. These results indicate that arginine vasopressin likely acts on neurons precedent to cardiac parasympathetic neurons and that arginine vasopressin likely acts not at the synaptic terminal but at the soma or dendrites of the precedent neuron. Oxytocin and agonists for the V(2)-arginine vasopressin and V(1b)-arginine vasopressin receptors had no effect. By contrast, the arginine vasopressin-evoked responses were completely abolished by a selective V(1a)-arginine vasopressin receptor antagonist indicating arginine vasopressin responses are mediated by V(1a)-arginine vasopressin receptors.We conclude that the V(1a)-arginine vasopressin receptor-mediated increase in frequency and amplitude of inhibitory GABAergic activity to cardiac parasympathetic neurons may be at least one mechanism by which central arginine vasopressin may increase heart rate and inhibit reflex bradycardia.     

丹参在抗肝细胞坏死中的钙拮抗作用

本工作在大鼠口服CCL_4所致肝细胞坏死模型上,比较了丹参与钙拮抗剂异搏定和扩血管药酚妥拉明对肝坏死的保护作用。结果发现,CCl_4引起的肝组织坏死与肝组织钙含量呈正相关(r=0.887,P<0.01)。丹参和异搏定使肝组织坏死程度减轻,肝组织钙含量减少,血浆GPT活性下降,肝组织匀浆MDA含量降低,细胞色素P-450活性升高。酚妥拉明组与损伤对照组比较,各项指标无明显差异。上述结果提示,丹参的作用效果优于异搏定。丹参抗CCl_4所致的肝细胞坏死井非通过扩血管作用,而是发挥其钙拮抗作用实现的。