清醒大鼠室旁核微量注射心房钠尿肽对压力感受性反射敏感性的影响

心房钠尿肽(atriaI natriuretic peptide,ANP)作为一种神经递质或调质可能参与心血管活动的中枢调节。本实验在清醒大鼠室旁核(paraventricular nucleus,PVN)注射ANP,探讨其对压力感受性反射敏感性的影响,并通过侧脑室注射血管升压素受体Ⅰ阻断剂OPC-21268,观察ANP对压力感受性反射敏感性的调节是否与中枢血管升压素有关。实验中观察到,在PVN内微量注射ANP(6、60 ng/0.2μl)可明显提高压力感受性反射敏感性(P<0.05),侧脑室预先注射OPC-21268 (0,45 μg/3 μl)后,ANP对压力感受性反射敏感性的增强作用明显减弱(P<0.05)。静脉注射ANP(60 ng/0.04 ml)不影响压力感受性反射敏感性。上述结果提示,心房钠尿肽对压力感受性反射活动起易化作用,心房钠尿肽的这种中枢作用可能部分通过中枢血管升压素介导。     

冷适应大鼠脑垂体、下丘脑、脾淋巴细胞和血浆β-内啡肽及其mRNA的变化

本文采用β-内啡肽(β-EP)mRNA打点杂交,反相高效液相色谱和放免测定研究了冷适应SD雄性大鼠垂体、下丘脑、淋巴细胞(LC)和血浆β-EP及其mRNA的变化,结果为:(1)冷暴一周时垂体β-EP mRNA明显增加,从而激活细胞免疫功能。(2)免疫中枢下丘脑和LC β-EP mRNA在冷适应建立(冷暴二周)时增加。(3)血浆β-EP从冷暴二周起持续增加,增强细胞免疫功能。虽然LC和血浆β-EP产物增加,但是垂体β-EP mRNA量从冷暴二周起恢复到对照组水平,很可能是通过LC-垂体-下丘脑轴,信息反馈到中枢神经系统造成的。     

猫颈部和腹部迷走神经加压反应的比较研究

刺激麻醉猫颈部和腹部迷走神经中枢端引起的升压反应,不但反应模式有别,其升压机制也不同。颈部迷走加压反应是在出现快速降压之后的一个缓慢持续的血压升高,而腹部迷走加压反应则是一个快而短暂的升压反应。在颈迷走加压反应出现的同时伴有血浆加压素(AVP)的增加,但血浆肾素活性(PRA)及血管紧张素 Ⅱ(ANG Ⅱ)和肾神经放电(RND)都有不同程度的下降。腹部迷走加压反应的出现则伴有 RND,PRA 和血浆 ANG Ⅱ 水平的增加,但 AVP 无明显改变。兴奋同一迷走神经颈腹段传入纤维引起的升压效应之所以不同主要是由于传入纤维的来源和在中枢的投射部位不同,因而升压机制也各异。     

人参茎叶皂甙对大鼠垂体催乳素分泌的影响及其机制的探讨

本实验观察了人参茎叶皂甙(GSLS)对雄性大鼠血浆催乳素水平、垂体催乳素细胞超微结构和下丘脑中枢神经递质的影响。结果表明:5～100mg/kg的GSLS可刺激催乳素的释放,剂量加大反而无效;GSLS还可拮抗急性饥饿所致的大鼠垂体催乳素细胞超微结构的损伤;GSLS能分别使大鼠下丘脑中多巴胺和5-羟色胺含量增高和降低。结果表明,GSLS有刺激垂体催乳素分泌的作用,其机制可能与其直接作用于垂体细胞和/或经下丘脑中多巴胺和5-羟色胺含量的变化有关。     

内毒素休克家兔脑区、脑脊液、血浆中脑啡肽含量的改变及纳洛酮的抗休克作用

本工作在戊巴比妥钠麻醉的家兔上进行。采用夹闭肠系膜上动脉阻断血流方法建立内毒紫休克的实验模型。用放射免疫分析法测定了休克前后脑区、脑脊液及血浆中脑啡肽含量的变化,并观察了脑室或静脉注射纳洛酮的抗休克效应。结果如下:1.休克时,下丘脑、延脑、桥脑的亮脑啡肽含量显著升高,中脑无明显变化、丘脑、纹状体下降。脑脊液和血浆中亮脑啡肽明显增加。外周静脉血与肾静脉血中无显著差别。2.侧脑室或静脉注射纳洛酮,均可使休克动物的血压回升,延长存活时间。脑室注射的升压数值略大,维持升压时间也较长。实验结果提示:脑啡肽参与内毒素休克过程。断阿片样物质的作用,可能是治疗内毒素休克的一个途径。     

大鼠松果腺中前列腺素含量与卵巢功能的关系的初步研究

用放射免疫法测定松果腺中 PGF_(2α)、PGE_1含量;用放射受体法测定外周血浆和垂体组织的 LH 含量。实验结果表明,在静止期用雌激素、卵巢切除和卵巢切除加用雌激素的大鼠,PG_S、LH 含量皆明显高于正常静止期含量(p<0.01);在卵巢切除加用孕激素的大鼠,PG_S、LH 含量明显低于卵巢切除大鼠含量(p<0.01);卵巢切除同时加用雌激素和孕激素的动物,则 LH 含量不增加,而松果腺中 PG_S 含量则仍然高于对照。可见外源性卵巢甾体激素的变化将导致松果腺中 PG_S 含量的变化,即小剂量雌激素可增加松果腺中 PG_S 的合成或释放,而孕激素则抑制松果腺中 PG_S 的合成或释放,同时与垂体 LH 的释放相似。松果腺中 PG_S 的作用机理,作者在讨论中指出的假设认为:松果腺中 PG_S 释放,可通过血液或脑脊液,作用于下丘脑、垂体,从而参予下丘脑-腺垂体-性腺轴的调节。     

应激性高血压大鼠脑干及下丘脑-垂体-肾上腺轴中肾上腺髓质素及其受体mRNA表达的改变

采用逆转录-聚合酶链式反应检测了慢性足底电击结合噪声应激致高血压大鼠下丘脑、延髓、中脑、垂体和肾上腺等组织中编码肾上腺髓质素的肾上腺髓质素前肽原(preproadrenomedullin,ppADM)基因以及ADM的特异性受体组件降钙素受体样受体(calcitonin-receptor-like receptor,CRLR)和受体活性调节蛋白2和3(receptor-activty-modifying proteins,RAMP2和RAMP3)表达的变化.我们观察到:与对照组相比,以3-磷酸甘油醛脱氢酶作为内参照,15 d足底电击结合噪声应激引起下丘脑、垂体和肾上腺中ppADM mRNA表达上调,而在延髓和中脑表达明显下调(P＜0.01或P＜0.05);CRLR基因表达量正常时在下丘脑相对较高,应激15 d后CRLR表达在延髓、中脑和下丘脑下调(P＜0.01或P＜0.05),而在垂体和肾上腺的表达无明显变化;应激后RAMP2基因在延髓和下丘脑表达上调,而在肾上腺表达显著下调(P＜0.01),其他部位无明显变化;RAMP3基因在对照组大鼠的中脑和下丘脑表达较高,在应激性高血压大鼠的下丘脑和垂体表达上调(P＜0.01或P＜0.05),而在中脑和肾上腺表达下调(P＜0.05),在延髓中的表达变化无统计学差异.上述结果提示:慢性足底电击结合噪声应激引起明显的中枢和下丘脑-垂体-肾上腺轴ADM及其受体组件CRLR/RAMP2或CRLR/RAMP3基因的表达变化.但慢性应激后中枢源性ADM及其受体的表达变化对应激和血压的调节以及在应激致高血压中的确切作用及机制尚待进一步研究.     

侧脑室注射牛磺酸对脑内生长抑素含量的影响

目的和方法：利用放射免疫分析技术,测定侧脑室注射不同浓度牛磺酸后１０ｍｉｎ、３０ｍｉｎ等不同时间内,大鼠部分脑区及血浆生长抑素含量的变化。结果：①侧脑室注射牛磺酸４０ｇ／Ｌ５μｌ１０ｍｉｎ后,垂体、下丘脑及桥延部生长抑素含量明显增加（Ｐ〈０．０５￣０．０１）;３０ｍｉｎ后,垂体、桥延部生长抑素含量恢复正常;②侧脑室注射４００ｇ／Ｌ５μｌ牛磺酸后,下丘脑生长抑系含量较对照组升高（Ｐ〈０．０５￣０．０     

脑内γ—氨基丁酸（GABA）在急性失血性低血压时对血压的影响

本实验通过大鼠和家兔侧脑室注射GABA受体阻断剂荷包牡丹碱(Bicuculline)研究正常血压和急性失血性低血压时,中枢GABA对血压的调节作用。结果表明:在两种情况下,荷包牡丹碱均有明显的升压作用,但后者显著大于前者,且这种升压效应不被去肾或去肾上腺所影响。同时发现:急性失血性低血压时,兔脑脊液中GABA含量明显增加,提示在急性失血性低血压时,中枢GABA具有阻止血压回升的作用,这种作用是通过对中枢交感神经系统的抑制引起的。     

应激性高血压犬鼠脑干及下丘脑-垂体-肾上腺轴中肾上腺髓质素及其受体mRNA表达的改变

采用逆转录- 聚合酶链式反应检测了慢性足底电击结合噪声应激致高血压大鼠下丘脑、延髓、中脑、垂体和肾上腺等组织中编码肾上腺髓质素的肾上腺髓质素前肽原(preproadrenomedullin, ppADM) 基因以及ADM 的特异性受体组件降钙素受体样受体(calcitonin-receptor-like receptor,CRLR)和受体活性调节蛋白2 和3(receptor-activity-modifying proteins, RAMP2 和RAMP3)表达的变化。我们观察到:与对照组相比,以 3- 磷酸甘油醛脱氢酶作为内参照,15 d 足底电击结合噪声应激引起下丘脑、垂体和肾上腺中ppADM mRNA表达上调,而在延髓和中脑表达明显下调(P<0.01 或 P<0.05); CRLR基因表达量正常时在下丘脑相对较高,应激15 d 后CRLR 表达在延髓、中脑和下丘脑下调(P<0.01 或 P<0.05), 而在垂体和肾上腺的表达无明显变化;应激后RAMP2 基因在延髓和下丘脑表达上调,而在肾上腺表达显著下调(P <0.01), 其他部位无明显变化;RAMP3 基因在对照组大鼠的中脑和下丘脑表达较高,在应激性高血压大鼠的下丘脑和垂体表达上调(P<0.01 或P<0.05), 而在中脑和肾上腺表达下调(P<0.05), 在延髓中的表达变化无统计学差异。上述结果提示:慢性足底电击结合噪声应激引起明显的中枢和下丘脑- 垂体-肾上腺轴ADM 及其受体组件CRLR/RAMP2 或CRLR/R     

Impaired water diuresis in a patient with pseudo-Bartter syndrome.

A 32-year-old man was diagnosed as having pseudo-Bartter syndrome due to surreptitious habitual vomiting and to maldigestion related to decayed teeth. His chief complaints were muscle pain and weakness. In this case, metabolic alkalosis, hypokalemia, hypochloremia, increased plasma renin activity and aldosterone levels were noticed with marked decreases in urinary chloride excretion. Creatinine clearance (GFR) and renal plasma flow (RPF) were also decreased. Blood pressure was normal, but the pressor response to angiotensin II was attenuated. Before treatment with 0.9% saline infusion, plasma vasopressin (AVP) was not suppressed sufficiently by lowering the plasma osmolality (Posm) with an oral water load (WL), but it normally responded to a rise in Posm due to hypertonic saline infusion. Moreover, plasma AVP was normally suppressed by WL after the replenishment of saline. Plasma atrial natriuretic peptide (ANP) was low before WL, but increased normally in response to WL. However, inconsistent with the normal response in this case, decreases in plasma AVP failed to dilute urinary osmolality and to increase urine flow, irrespective of the levels of plasma ANP. These results indicate that chronic inanition due to surreptitious vomiting causes impaired renal diluting ability through decreases in GFR and RPF, irrespective of the levels of plasma AVP and ANP.     

Effect of cerebrospinal fluid hyperosmolality on sweating in the heat-stressed patas monkey

Dehydration increases the osmolality of body fluids and decreases the rate of sweating during thermal stress. By localizing osmotic stimuli to central nervous system tissues, this study assessed the role of central stimulation on sweating in a heat-stressed nonhuman primate. Lenperone-tranquilized patas monkeys (Erythrocebus patas n = 5), exposed to 41 +/- 2 degrees C, were monitored for calf sweat rate, rectal and mean skin temperatures, oxygen consumption, and heart rate during infusions (255-413 microliters) of hypertonic artificial cerebrospinal fluid (ACSF) into the third cerebral ventricle. ACSF made hypertonic with NaCl to yield osmolalities of 800 and 1,000 mosmol/kgH2O significantly decreased sweat rate compared with control ACSF (285 mosmol/kgH2O), achieving maximal reductions during infusion of 37 and 53%, respectively. Rectal temperature significantly increased during the recovery period, reaching elevations of 0.69 and 0.72 degrees C, respectively, at 20 min postinfusion. In contrast, ACSF made hypertonic with sucrose (800 mosmol/kgH2O) failed to change sweat rate or rectal temperature during infusion in three animals. Thus, intracerebroventricular infusions of hypertonic ACSF mimicked dehydration-induced effects on thermoregulation. The reduction in heat loss during infusion appeared to depend on an elevation in cerebrospinal fluid [Na+] and not osmolality per se.     

Stress and water balance: the roles of ANP, AVP and isatin

Stress is often associated with water retention and its resolution with diuresis. The biological systems for the control of stress and water balance are very closely related. Corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) are co-localised in the hypothalamus and often act synergistically. Atrial natriuretic peptide (ANP) can exert a feedback control on the hypothalamic/pituitary/adrenal axis. ANP has been shown to be anxiolytic, whereas AVP may be anxiogenic. AVP and ANP levels have been found to be abnormal in a range of stress disorders and psychiatric illnesses. Isatin is an endogenous anxiogenic factor which is also a potent inhibitor of the ANP receptor. It may provide a link between the function of monoamines during stress, and the control of water balance by ANP.     

Pathogenesis of extracellular fluid abnormalities of hypothalamic hypodipsia-hypernatremia syndrome

A 26-year-old man with hypothalamic hypodipsia-hypernatremia syndrome is reported, who presented with adipsia, hypernatremia, and impaired osmolality-mediated arginine vassopressin (AVP) secretion. A chorionic gonadotropin-secreting tumor was detected in the anterior hypothalamus and treated with external irradiation. After the treatment, hypernatremia persisted and was not corrected by fluid loading, osmolality-mediated AVP secretion remained impaired. Despite the absence of signs of hydropenia, hypovolemia was suggested by low blood pressure and elevated plasma indices of the renin-angiotensin system, and supported by blood volume determination. The plasma aldosterone concentrations were inappropriately low for the renin-angiotensin status. The plasma atrial natriuretic polypeptide (ANP) level was normal in spite of hypovolemia and increased more than double after fluid loading. Hypernatremia, primarily caused by hypodipsia and impaired osmolality-mediated AVP secretion, secondarily sustained ANP secretion and suppressed aldosterone release, which conceivably contributed to the development and perpetuation of hypovolemia in this patient.     

Effect of high and low sodium intake on urinary aquaporin-2 excretion in healthy humans

The degree of water transport via aquaporin-2 (AQP2) water channels in renal collecting duct principal cells is reflected by the level of the urinary excretion of AQP2 (u-AQP2). In rats, the AQP2 expression varies with sodium intake. In humans, the effect of sodium intake on u-AQP2 and the underlying mechanisms have not previously been studied. We measured the effect of 4 days of high sodium (HS) intake (300 mmol sodium/day; 17.5 g salt/day) and 4 days of low sodium (LS) intake (30 mmol sodium/day; 1.8 g salt/day) on u-AQP2, fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), urinary excretion of PGE(2) (u-PGE(2)) and cAMP (u-cAMP), and plasma concentrations of vasopressin (AVP), renin (PRC), ANG II, aldosterone (Aldo), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in a randomized, crossover study of 21 healthy subjects, during 24-h urine collection and after hypertonic saline infusion. The 24-h urinary sodium excretion was significantly higher during HS intake (213 vs. 41 mmol/24 h). ANP and BNP were significantly lower and PRC, ANG II, and Aldo were significantly higher during LS intake. AVP, u-cAMP, and u-PGE(2) were similar during HS and LS intake, but u-AQP2 was significantly higher during HS intake. The increases in AVP and u-AQP2 in response to hypertonic saline infusion were similar during HS and LS intake. In conclusion, u-AQP2 was increased during HS intake, indicating that water transport via AQP2 was increased. The effect was mediated by an unknown AVP-independent mechanism.     

Naloxone effect on ANP in trained and untrained rats

1. The effect of a dose of naloxone (1 mg·kg⁻¹ b.w.) on peripheral (plasma, atria) and central (hypothalamus, hypophysis) levels of atrial natriuretic peptide (ANP) was investigated in the rat.2. In control rats, an acute subcutaneous dose of naloxone produced no significant change in plasma ANP, but a decrease (NS) in atrial ANP concentration.3. In physically conditioned animals, naloxone produced a significant decrease in atrial ANP levels. Receptor sensitivity may thus be involved in this differential response.4. In hypothalamus and hypophysis, no effect on ANP concentrations was seen after a high dose of naloxone whether in control or in physically conditioned animals, suggesting peripheral and central ANP might be differently regulated, at least after chronic endurance physical training.     

Effect of vasopressin and V1 receptors blockade on hypotensive action of ANP in normotensive (WKY) and spontaneously hypertensive rats.

The aim of the study was to find out whether vasopressin (AVP) modifies hypotensive and heart rate accelerating effects of atrial natriuretic peptide (ANP) in normotensive (WKY) and spontaneously hypertensive (SHR) conscious rats. The effect of i.v. administration of 1; 2 and 4 micrograms of ANP on blood pressure (MP) and heart rate (HR) was compared during i.v. infusion of 0.9% NaCl (NaCl), NaCl+AVP (1.2 ng kg-1 min-1) and NaCl+dEt2AVP (V1 receptors antagonist, 0.5 microgram kg-1 min-1). AVP increased MP in SHR and WKY and decreased HR in SHR. V1 antagonist decreased MP and increased HR only in SHR. In SHR ANP decreased MP and increased HR during NaCl, AVP and V1 antagonist infusion. In WKY these effects were observed only during AVP administration. In each experimental situation hypotension and tachycardia induced by ANP were greater in SHR than in WKY. In both strains ANP induced changes in MP and HR were enhanced during AVP in comparison to NaCl infusion. V1 antagonist did not modify effects of ANP in WKY and SHR. The results indicate that ANP abolishes hypertensive response induced by blood AVP elevation and that the basal levels of endogenous vasopressin acting through V1 receptors does not interfere with hypotensive action of ANP neither in WKY nor in SHR.     

Naloxone effect on ANP in trained and untrained rats.

1. The effect of a dose of naloxone (1 mg.kg-1 b.w.) on peripheral (plasma, atria) and central (hypothalamus, hypophysis) levels of atrial natriuretic peptide (ANP) was investigated in the rat. 2. In control rats, an acute subcutaneous dose of naloxone produced no significant change in plasma ANP, but a decrease (NS) in atrial ANP concentration. 3. In physically conditioned animals, naloxone produced a significant decrease in atrial ANP levels. Receptor sensitivity may thus be involved in this differential response. 4. In hypothalamus and hypophysis, no effect on ANP concentrations was seen after a high dose of naloxone whether in control or in physically conditioned animals, suggesting peripheral and central ANP might be differently regulated, at least after chronic endurance physical training.     

侧脑室注射心房钠尿肽对大鼠室旁核单位放电的影响

本实验利用微电极技术在大鼠下丘脑共记录到118个自发放电单位,其中84个位于室旁核(PVN)内,34个位于 PVN 邻近部位。侧脑室注入心房钠尿肽(ANP)后,受其影响的 PVN神经元和 PVN 邻近部位神经元,分别有91%(P<0.005)和71%(P>0.05)表现为自发放电频率减少;侧脑室注入高渗 NaCl 溶液则分别使64.7%(P<0.005)和61.1%(P>0.05)的神经元自发放电频率增加。结果表明,侧脑室注入 ANP 对 PVN 神经元自发放电活动具有明显的抑制作用。     

Clinical features, diagnosis and molecular studies of familial central diabetes insipidus

BACKGROUND: Familial central diabetes insipidus (DI) is rare and is characterised by polydipsia and polyuria with a variable age of onset. The evaluation of arginine vasopressin (AVP) secretion in these individuals has been reported infrequently and only in adulthood. OBJECTIVE: To describe the clinical features, diagnosis and molecular investigation of children affected by familial central DI. METHODS: Functional studies of AVP secretion were undertaken in children from two kindreds with familial central DI. The AVP-neurophysin II (AVP-NPII) gene was also sequenced in symptomatic individuals. RESULTS: In affected individuals, the result of the water deprivation test may be inconclusive. However, the hypertonic saline test identified both the severe and partial forms of AVP deficiency. A novel mutation of the AVP-NPII gene was identified by direct gene sequencing in both families. CONCLUSIONS: This report highlights the progressive decline in AVP secretion with increasing age in this disorder and the usefulness of mutational analysis in these families. In symptomatic individuals, the hypertonic saline test may be a useful second-line investigation for functional studies of AVP secretion where molecular diagnostics are unavailable.