Arginine vasopressin as a target in the treatment of acute heart failure

Congestive heart failure(CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1 a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis(free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.

ARGININE VASOPRESSIN GENE EXPRESSION IN SUPRAOPTIC NUCLEUS AND PARAVENTRICULAR NUCLEUS OF HYPOTHALAMOUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION

Background. Our previous studies indicated that the increased arginine vasopressin(AVP) in ischemic brain regions of gerbils could exacerbate the ischemic brain edema. This experiments is further clarify the relation between AVP and cerebral ischemia at the molecular level. Methods. The contents of AVP, AVP mRNA, AVP immunoreactive(ir) neurons in supraoptic nucleus(SON) and paraventricular nucleus(PVN) after cerebral ischemia and reperfusion were respectively determined by radioimmunoassay(RIA), immunocytochemistry(ⅡC), situ hybridization and computed image pattern analysis. Results. The contents of AVP in SON, PVN were increased, and the AVP ir positive neurons in SON and PVN were also significantly increased as compared with the controls after ischemia and reperfusion. And there were very light staining of AVP ir positive neurons in the other brain areas such as suprachiasmatic nucleus (SC) and periventricular hypothalamic nucleus (PE), but these have no significant changes as compared with the controls. During different periods of cerebral ischemia (30～120 min) and reperfusion (30 min), AVP mRNA expression in SON and PVN were more markedly increased than the controls. Conclusions. The transcription of AVP gene elevated, then promoting synthesis and release of AVP in SON, PVN. Under the specific condition of cerebral ischemia and reperfusion, the activity and contents of central AVP increased abnormally is one of the important factors which causes ischemia brain damage.

Aquaporin-4 in the formation of cerebral edema following severe burns What role do arginine vasopressin levels play?

BACKGROUND： Aquaporin-4 （AQP-4）, which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain injury. However, the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown. OBJECTIVE： To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin （AVP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS： Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS： A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points： 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100℃ water for 15 seconds to induce grade III bum injury that measures 30% of total bum surface area. MAIN OUTCOME MEASURES： Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS： Brain water content gradually increased following severe burn injury. AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, hippocampus, choroid plexus, and cerebral cortex. Plasma AVP levels increased following burn injury. AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema （r= 0.870, 0.848, P 〈 0.01）. CONCLUSION： AQP-4 participated in the formation of cerebral edema following burn injury. Plasma AVP upregulated AQP-4 expression in brain tissue, thereby promoting formation of cerebral edema.

Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.

基于“肾主水”探讨AVP-V2R-AQP2轴与肾病阴虚水肿的关系

肾病阴虚水肿常见于肾脏病中、后期患者,有着难治性、顽固性的特点,并且随着病情进展、利尿药物的应用而逐渐加重,临床关注度低,治疗措施有限,治疗效果不佳。血管升压素(AVP)-加压素受体2(V2R)-水通道蛋白2(AQP2)轴是机体调节水盐平衡的关键通路,且与肾脏排泄钠失常直接相关。根据中医“象”思维,认为“肾主水”理论推导的肾病阴虚水肿发病机制与AVP-VR2-AQP2轴导致肾病阴虚水肿相类似。故本文将基于“肾主水”理论,结合王悦芬教授临床经验,从中、西医不同的角度及运用中医药调控AVP-VR2-AQP2轴治疗肾病阴虚水肿等方面,深入探讨“肾主水”、AVP-V2R-AQP2轴、肾病阴虚水肿三者之间的联系,进一步认识“肾主水”机制,探讨AQP2作为肾病阴虚水肿新型生物标志物的可能,为肾病阴虚水肿的治疗提供新思路,为中医药现代化研究提供可靠依据。

Expression of hippocampal corticosteroid receptors,as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus,in fornix transected rats

BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.

Vasopressin in vasoplegic shock:A systematic review

BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vasopressin has increasingly been usedas a primary pressor in vasoplegic shock because of its unique pharmacology andlack of inotropic activity. It remains unclear whether vasopressin has distinctbenefits over standard of care for patients with vasoplegic shock.AIMTo summarize the available literature evaluating vasopressin vs non-vasopressinalternatives on the clinical and patient-centered outcomes of vasoplegic shock inadult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegicshock after cardiac surgery. Randomized controlled trials, prospective cohorts,and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine,methylene blue, hydroxocobalamin, or other pressors were included. The primaryoutcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke,ICU length of stay, duration of vasopressor therapy, incidence of acute kidneyinjury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusioncriteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality,stroke, ventricular arrhythmias, and duration of mechanical ventilation weresimilar between groups. Conflicting results were observed for acute kidney injurystage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of staywith higher certainty of evidence in favor of vasopressin serving a protective rolefor these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any ofthe included outcomes. Results are limited by mixed methodologies, small overallsample size, and heterogenous populations.

Effect of instant moxibustion on the levels of prostaglandin and arginine vasopressin in the uterine tissues of dismenorrhea rats with cold-damp congealing and stagnation type

Objective To observe the effect of instant moxibustion on the levels of prostaglandin E_2（PGE_2）,prostaglandin F2α（PGE_（2α）） and arginine vasopressin（AVP） in the uterine tissues of dismenorrhea rats with cold-damp congealing and stagnation type and to explore its possible mechanism.Methods Female Wistar rats were randomly divided into blank group,model group,herble medicine group,pre-moxibustion group and instant moxibustion group,with 9 rats in each group.Cold-damp congealing and stagnation type primary dismenorrhea models were established by adopting（0±1）℃ ice waterextraction method combined with estradiol benzoate injection method.After modeling on the 8th day,in herble medicine group,Tongjingbao granules was given to the rats by intragastric administration.In pre-moxibustion group,mild moxibustion was carried out at ＂Shénquè＂（神阙 CV 8） and ＂Guānyuán＂（关元 CV 4） of the rats for 10 min at each acupoint.In instant moxibustion group,moxibustion as that in pre-moxibustion group was conducted for once after injection with oxytocin on the 11 th day.ELISA was adopted to detect the levels of PGE_2 and PGE_（2α） in the uterine tissues of rats,and radioimmunoassay was used for detection of AVP level in the uterine tissues of rats.Results Compared with the model group,the latent period of rats in herbal medicine group,premoxibustion group and instant moxibustion group obviously prolonged,the number of times of torsion reduced,and the total score of torsion decreased（P0.01）;compared with herbal medicine group,the latent period of rats in instant moxibustion group obviously prolonged,and the total score of torsion decreased（P0.05 or P0.01）;compared with pre-moxibustion group,the number of times of torsion of rats in instant moxibustion group reduced,and the total score of torsion decreased（P0.01）.Compared with blank group,the levels of PGE_（2α） and AVP and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in model group significantly increased（P0.01）,and the PGE_2 level significantly reduced（P0.01）;compared with model group,the PGE_（2α） level and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in herble medicine group,pre-moxibustion group and instant moxibustion group obviously reduced（P0.05 or P0.01）,the PGE_2 level obviously increased（P0.01）,and the AVP level in the uterine tissues of rats in pre-moxibustion group and instant moxibustion group obviously reduced（P0.05 or P0.01）;compared with herbal medicine group,the levels of PGE_（2α） and AVP and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in instant moxibustion group significantly reduced（P0.05 or P0.01）;compared with pre-moxibustion group,the PGE_（2α） level and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in instant moxibustion group obviously reduced（P0.05）,and the PGE_2 level obviously increased（P0.01）.Conclusion Both pre-moxibustion and instant moxibustion can obviously inhibit spasmodic uterine smooth muscle contraction of rats with dismenorrhea,regulate imbalanced levels of PGE_（2α） and PGE_2,reduce the AVP level,so as to improve the uterine hypoxia-ischemia,and play a role in alleviating pain.The efficacy of instant moxibustion was superior to that of pre-moxibustion.

Blood pressure and atherosclerosis

930082 Clinical administration of atrial natri-uretic factor in reno-vascular hypertension.ZHANG Weiguo(张卫国),et al.Cardiovasc In-stit & Fuwai Hosp,CAMS,Beijing.Chin Cir J1992;7(5):450-452.In order to evaluate the effects of atrial natri-uretic factor(ANF)on patients with reno-vas-cular hypertension,α-hANF(0.025μg/kg/min×60min)was administered to 7 patients byi.v.drip..The renin-angiotensin-aldosteronesystem,plasma catecholamine and arginine va-sopressin were suppressed with diuresis and na-triuresis and lowering of blood pressure.

升压物质检查法在药品生物安全性检查中的应用及实验关键点

升压物质检查法是《中国药典》收录的一项药物安全性检查法。用以检测可能含有引起血压升高杂质的原料药及其制剂中升压物质的限度是否符合标准规定。该检查法的使用范围虽然较窄,但在临床用药安全上发挥着重要作用。本文就升压物质检查法的实验原理、实验系统、方法应用、各国药典收录情况、改进建议,以及实验要点进行综述,为相关实验人员提供参考。

醋酸去氨加压素对丝裂原活化蛋白激酶磷酸酶-1在大鼠耳蜗的表达及功能研究

目的检测醋酸去氨加压素(deamino arginine vasopressin,DDAVP)作用后丝裂原活化蛋白激酶磷酸酶-1(mitogen-activated protein kinase phosphatase,MKP-1)在大鼠耳蜗组织的表达情况,探讨MKP-1是否参与梅尼埃病的发生。方法选取SPF级雄性SD大鼠20只,随机分为实验组和对照组,每组10只。实验组腹腔注射DDAVP,对照组腹腔注射等量0.9%氯化钠溶液。造模结束后行听性脑干反应(auditory brainstem response,ABR)检测听力,苏木精-伊红染色观察耳蜗形态变化,免疫组织化学及蛋白质免疫印迹检测MKP-1在耳蜗的表达位置及定量分析。结果实验组ABR阈值较造模前上升约10 dB,差异有统计学意义(P<0.01);实验组耳蜗切片苏木精-伊红染色出现膜迷路积水表现,实验组积水率达80%;免疫组织化学显示,MKP-1广泛表达于血管纹、螺旋韧带、螺旋缘、柯蒂器、以及螺旋神经节。两组血管纹、螺旋韧带及螺旋神经节表达比较,差异均有统计学意义(P<0.05);两组SLM和OC表达比较,差异无统计学意义(P>0.05)。蛋白质免疫印迹显示,实验组MKP-1表达低于对照组,差异有统计学意义(P<0.01)。结论DDAVP可能通过下调MKP-1促进膜迷路积水形成,进而参与梅尼埃病的发病过程。

当归芍药散对肾病综合征大鼠水肿的改善作用及机制

目的探究当归芍药散对肾病综合征大鼠水肿的改善作用及作用机制。方法将大鼠随机分为正常组、模型组、当归芍药散组(17.2 g·kg^(-1)·d^(-1))、氯沙坦组(30 mg·kg^(-1)·d^(-1))、托伐普坦组(3 mg·kg^(-1)·d^(-1))。尾静脉注射阿霉素建立肾病综合征大鼠模型。给药4周后,检测各组大鼠肾功能指标及24 h尿蛋白含量变化;免疫组化法检测肾组织中水通道蛋白2(aquaporin 2,AQP2)和pS256-AQP2的分布;放射免疫法测定血浆精氨酸加压素(arginine vasopressin,AVP)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)水平;Western blot和RT-PCR法分别检测肾脏AQP2、pS256-AQP2、血管紧张素1型受体(angiotensin type 1 receptor,AT1R)、精氨酸加压素受体2(arginine vasopressin receptor 2,V2R)蛋白及mRNA的表达。结果3种药物均可改善肾病综合征大鼠肾功能,减轻蛋白尿,降低血浆AVP及AngⅡ水平,下调AQP2、pS256-AQP2蛋白和mRNA表达。当归芍药散与托伐普坦对于降低血浆AVP水平的效果优于氯沙坦。结论当归芍药散可能通过降低AVP及AngⅡ水平,进而调节AQP2的表达,改善肾病综合征大鼠水肿。

非对称性二甲基精氨酸在不明原因复发性流产患者绒毛及外周血的表达及其意义

目的 探讨不明原因复发性流产(URSA)患者绒毛及外周血非对称性二甲基精氨酸(ADMA)表达及其临床价值。方法 选取URSA患者168例,采用计算机产生随机数法将就诊患者以3∶1的比例分为训练集126例(URSA组)和测试集42例,另选取同期于我院进行终止妊娠的126例孕妇作为对照,对比训练集及对照组临床资料及外周血和绒毛组织ADMA表达,通过拟合曲线和阈值效应分析患者血清URSA表达与URSA发生的关系,采用多因素Logistics回归模型分析发生URSA的独立危险因素,构建列线图模型。结果 与对照组比较,URSA组患者IL-6、IL-117、Th17、Th17/Treg及血浆、绒毛组织ADMA表达显著增加,孕酮、IL-10、TGF-β及Treg显著降低(P<0.05)。IL-6、IL-17、Th17、Th17/Treg及血浆ADMA、绒毛组织ADMA是发生URSA的独立危险因素,而IL-10、TGF-β及Treg是发生URSA的保护因素(P<0.05)。当血浆ADMA≥1.43μmol/L时,血浆ADMA每增加0.6μmol/L,孕妇发生VRSA的风险增加17%,差异具有统计学意义(OR=0.115,95%CI:0.102~0.133,P<0.05);当绒毛ADMA≥1.92μmol/L时,绒毛ADMA每增加0.6μmol/L,孕妇发生URSA的风险增加14%,差异具有统计学意义(OR=1.192,95%CI:1.085~1.302,P<0.05)。依据独立影响因素构建的列线图预测模型具有较高的区分度、准确性和临床适用性。结论 ADMA在URSA患者血浆及绒毛组织中的表达增加,是URSA发生的独立危险因素,对URSA的发生具有一定的预测价值。

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Endolymphatic Hydrops

Objective: To investigate the effects of electroacupuncture(EA) on endolymphatic hydrops(EH) and the regulation of arginine vasopressin(AVP)-aquaporin-2(AQP2) pathway in guinea pigs. Methods: EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui(GV 20) and Tinggong(SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin(HE) staining, and then the ratio of scala media(SM) area to SM + scala vestibuli(SV) area(R value) was calculated. In mechanical studies, a comparison of plasma AVP(p-AVP) concentrations, cyclic adenosine monophosphate(cAMP) levels, vasopressin type 2 receptor(V2R) and AQP2 mRNA expressions in the cochlea were compared among groups. Results: EA significantly reduced cochlear hydrops in guinea pigs(P=0.001). EA significantly attenuated the AVPinduced up-regulation of p-AVP concentrations(P=0.006), cochlear c AMP levels(P=0.003) and AQP2 mRNA expression(P=0.016), and up-regulated the expression of V2R mRNA(P=0.004) in the cochlea. Conclusion: The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.

Effect of electroacupuncture on arginine vasopressin-induced endolymphatic hydrops

OBJECTIVE: To investigate the influence of electroacupuncture(EA) on experimentally induced endolymphatic hydrops(EH) in guinea pigs, and elucidate the association between the dehydrating effect of EA and changes in stria vascularis ultrastructure and expression of vasopressin type 2 receptor(V2R), cyclic adenosine monophosphate(cAMP),and aquaporin 2(AQP2) in the endolymphatic sac(ES).METHODS: The EH model was established by intraperitoneal injection of arginine vasopressin(AVP).As a treatment, EA was delivered to Baihui(GV 20)and Tinggong(SI 19) acupoints, once daily for 10 consecutive days. For histomorphological studies,degree of cochlear hydrops was evaluated by hematoxylin-eosin staining, and the ratio of scala media(SM) area to SM + scala vestibuli area was calculated. In mechanical studies, ultrastructural changes in stria vascularis tissue were examined by transmission electron microscopy. In addition, cAMP levels and mRNA expression levels of V2 R and AQP2 in the ES were compared among groups.RESULTS: EA treatment significantly reduced cochlear hydrops compared with hydropic guinea pigs(P = 0.015). Furthermore, EA attenuated ultrastructural changes in the stria vascularis tissue following EH, significantly upregulated the expression of V2 R(P = 0.016), and attenuated AVP-induced upregulation of both cAMP(P = 0.038) and AQP2 expression(P = 0.017) in the ES.CONCLUSION: Collectively, the results of the present study suggest that the dehydrating effect of EA is associated with improvement of stria vascularis ultrastructure and V2 R-cAMP-AQP2 signaling pathway regulation in the ES.

Early changes of endothelin,nitric oxide and arginine-vasopressin in patients with acute cerebral injury

Objective: To investigate the early changes and clinical significance of plasma endothelin (ET), nitric oxide (NO) and arginine vasopressin (AVP) in patients with acute moderate or severe cerebral injury. Methods: The early (at 24 hours after injury) plasma concentrations of ET, NO and AVP were measured with radioimmunoassay and Green technique in 48 cases of acute moderate (GCS≤8 in 27cases ) or severe (GCS>8 in 21 cases) cerebral injury (Group A), in 42 cases of non cerebral injury (Group B) and in 38 normal individuals (Group C), respectively. Results: The early plasma concentrations of ET ( 109.73 ng/L±12.61 ng/L ), NO ( 92.82 μmol/L± 18.21 μmol/L ) and AVP ( 49.78 ng/L±14.29 ng/L ) in Group A were higher than those in Group B ( 67.90 ng/L ±11.33 ng/L , 52.66 μmol/L±12.82 μmol/L and 29.93 ng/L±12.11 ng/L , respectively, P<0.01 ) and Group C ( 50.65 ng/L±17.12 ng/L , 36.12 μmol/L ±12.16 μmol/L and 5.18 ng/L ± 4.18 ng/L , respectively, P<0.001 ). The amounts of ET, NO and AVP in patients with severe cerebral injury were 116.18 ng/L± 18.12 ng/L , 108.19 μmol/L±13.28 μmol/L and 58.13 ng/L±16.78 ng/L , respectively, which were significantly higher than that of the patients with moderate cerebral injury ( 92.33 ng/L±16.32 ng/L , 76.38 μmol/L ±12.71 μmol/L and 36.18 ng/L±12.13 ng/L respectively, P<0.01 ). The early levels of ET, NO and AVP in Group A were negatively related to the GCS scales. The amounts of ET, NO and AVP were 126.23 ng/L± 15.23 ng/L , 118.18 μmol/L±10.12 μmol/L and 63.49 ng/L±14.36 ng/L respectively in patients with subdural hematoma, which were significantly higher than those in patients with epidural hematoma ( 81.13 ng/L ±12.37 ng/L , 68.02 μmol/L±13.18 μmol/L and 45.63 ng/L±12.41 ng/L respectively, P<0.01 ). The plasma concentrations of ET, NO and AVP in stable duration (at 336 hours after injury) in Group A and Group B were similar to those in Group C. Conclusions: ET, NO and AVP were related to the pathophysiological process that occurs in the early stage of acute cerebral injury and the values of ET, NO and AVP correlate positively with the clinical manifestations. The changes of plasma ET, NO and AVP can be regarded as important indices to assess the severity of acute cerebral injury.

Changes of arginine vasopressin in elderly patients with acute traumatic cerebral injury

Objective: To investigate the changes and clinical significance of arginine vasopressin (AVP) in elderly patients with acute traumatic cerebral injury. Methods: With radioimmunoassay, the plasma levels of AVP were measured in 32 elderly patients with acute traumatic cerebral injury, 30 traumatic patients without cerebral injury and 30 healthy elderly volunteers, respectively. Results: The plasma level of AVP in patients with acute traumatic cerebral injury in the early stage ( 48.30 ng/L±8.28 ng/L ) was much higher than that of the traumatic patients without cerebral injury ( 25.56 ng/L±4.64 ng/L , P< 0.01 ), which was much higher than that of the healthy volunteers ( 5.06 ng/L±4.12 ng/L , P< 0.01 ). The level of AVP in the patients with acute traumatic cerebral injury was negatively related with GCS scores. Conclusions: AVP may play an important role in the pathophysiological process in patients with acute traumatic cerebral injury in the early stage. The severer the cerebral injury is, the higher the level of AVP is, which indicates that the level of AVP may be one of the severity indices of traumatic cerebral injury in elderly patients.

Growth hormone promotes the reconstruction of injured axons in the hypothalamo-neurohypophyseal system

Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

Early changes of arginine vasopressin and angiotensin II in patients with acute cerebral injury

Objective: To study the changes and clinical significance of arginine vasopressin (AVP) and angiotensin II (AT II) in patients with acute moderate and severe cerebral injury. Methods: The early plasma concentration was checked by radioimmunoassay in 47 cases of acute moderate and severe cerebral injury, 30 cases of non cerebral injury and 30 healthy volunteers. Results: The early plasma concentrations of AVP ( 50.23 ng/L± 15.31 ng/L) and AT II ( 248.18 ng/L± 82.47 ng/L) in cerebral injury group were higher than those in non cerebral injury group (AVP for 30.91 ng/L± 11.48 ng/L and AT II for 120.67 ng/L± 42.49 ng/L, P< 0.01 ). The early plasma concentrations of AVP and AT II in cerebral injury group were also obviously higher than those of the volunteers (AVP for 5.16 ng/L± 4.23 ng/L and AT II for 43.11 ng/L± 16.39 ng/L, P< 0.001 ). At the same time, the early plasma level of AVP ( 58.90 ng/L± 18.12 ng/L) and AT II ( 292.13 ng/L± 101.17 ng/L) was higher in severe cerebral injured patients than moderate cerebral injured ones (AVP for 36.68 ng/L± 12.16 ng/L and AT II for 201.42 ng/L± 66.10 ng/L, P< 0.01 ). The early level of AVP and AT II was negatively related to the GCS scales in acute cerebral injury. The early plasma concentrations of AVP ( 45.98 ng/L± 13.48 ng/L) and AT II ( 263.28 ng/L± 80.23 ng/L) were lower in epidural hematoma group than those of subdural hematoma and cerebral injury group (AVP for 64.12 ng/L± 15.56 ng/L and AT II for 319.82 ng/L± 108.11 ng/L, P< 0.01 ). Conclusions: AVP and AT II may play an important role in pathophysiologic process in the secondary cerebral injury. The more severe the cerebral injury is, the higher the early level of AVP and AT II will be. The early plasma level of AVP and AT II may be one of the severity indexes of cerebral injury.

Early change of plasma and cerebrospinal fluid arginine vasopressin in traumatic subarachnoid hemorrhage

Objective： To investigate the changes and effects of arginine vasopressin （AVP） in patients with acute traumatic subarachnoid hemorrhage （tSAH）. Methods： The plasma and cerebrospinal fluid （CSF） level of AVP, and intracranial pressure （ICP） were measured in a total of 21 patients within 24 hours after tSAH. The neurological status of the patients was evaluated by Glasgow Coma Scale （GCS）. Correlation between AVP and ICP, GCS was analyzed respectively. Meanwhile, 18 healthy volunteers were recruited as control group. Results： Compared with control group, the levels （pg/ml） of AVP in plasma and CSF （x±s） in tSAH group were significantly increased within 24 hours （38.72±24.71 vs 4.54±1.38 and 34.61±21.43 vs 4.13± 1.26, P〈0.01）, and was remarkably higher in GCS ≤8 group than GCS〉8 group （50.96±36.81 vs 25.26±12.87 and 44.68±31.72 vs 23.53±10.94, P〈0.05）. The CSF AVP level was correlated with ICP （r= 0.46, P〈0.05）, but no statistically significant correlation was found between plasma AVP, CSF AVP and initial GCS （r= -0.29, P〉0.05 and r= -0.32, P〉0.05, respectively）. The ICP （ram Hg） in tSAH patients was elevated and higher in GCS ≤ 8 group than in GCS〉8 group （25.9±9.7 vs 17.6±5.2, P〈0.05）. Conclusion： Our research suggests that AVP is correlated with the severity oftSAH, and may be involved in the pathophysiological process of brain damage in the early stage after tSAH. It seems that compared with the plasma AVP concentration, CSF AVP is more related to the severity oftSAH.