Vascular effects, formation, clearance and release of endothelin peptides in the pig

The formation, release, clearance and vascular effects of endothelin (ET)-like immunoreactivity (-LI) was studied in the pig in vivo. Intravenous infusion of ET-1, 2 and 3 (20 pmol/kg/min for 20 min) increased vascular resistance in the kidney, spleen and skeletal muscle. The most pronounced effects were evoked by ET-1 which caused increases in renal, splenic and skeletal muscle vascular resistance of 554, 528 and 38%, respectively, and a threshold response was observed at 80 pmol/l ET-LI in arterial plasma. During the infusion a large portion of arterial plasma, ET-LI was cleared over the kidney, spleen and skeletal muscle, whereby the most pronounced clearance was observed for ET-1 (73–93%). The ET-1 precursor Big-ET (1–39) given in a similar dose produced only a slight increase in renal vascular resistance (by 20%) and was cleared only over the kidney and not over the spleen or skeletal muscle. Using an ET-1 specific antiserum it was found that plasma ET-1 levels increased 11-fold during the infusion of Big-ET, indicating formation of ET-1 from Big-ET. The half-lives of circulating ET-1, 2 and 3 were 1.3–2.1 min and of Big-ET 8.9 min. Induction of asphyxia for 2 min increased the overflow of ET-LI from the spleen, suggesting local release, and caused splenic vasoconstriction. During i.v. administration of endotoxin for 4 h, arterial plasma ET-LI increased 7-fold and renal and splenic vasoconstrictor responses developed that correlated significantly with the arterial plasma ET-LI. Furthermore, a local release of ET-LI in the spleen was observed during endotoxin administration. Chromatographic characterization of the ET-LI in plasma during endotoxin administration revealed presence of ET-1 and Big-ET. It is concluded that there exists specificity both concerning the vasoconstrictor effects and removal from the circulation of ET peptides, both mechanisms being most prominent for ET-1 in the kidney. Furthermore ET-1 seems to be formed from circulating Big-ET and release of ET-LI can be detected during situations like asphyxia and sepsis.     

Hemoglobin concentration of pastoral nomads permanently resident at 4,850-5,450 meters in Tibet

This paper presents data on the hemoglobin concentration of a sample of 103 pastoral nomads who are lifelong residents of Phala, at 4,850-5,450 m, on the northern plateau of the Tibet Autonomous Region of the Peoples' Republic of China. This native population resides at the highest altitude of which we are aware and is thus exposed to the most extreme chronic hypoxic stress. However, they do not exhibit the most pronounced physiological adaptations, i.e., hemoglobin concentrations exceeding those found in all other high-altitude populations. Adult male and female mean hemoglobin concentrations of 18.2 and 16.7 gm/dl, respectively, were found. These data, in conjunction with earlier studies of ethnic Tibetans living at 3,400 m, demonstrate a pattern of increasing hemoglobin concentration (erythrocytosis) at increasing altitude of residence in the Himalayas and Tibet. At the same time, however, the hemoglobin concentration is lower than that found among Andean highlanders. These new data raise the possibility of quantitative population differences in hematological adaptation to high altitude hypoxia.     

Ventilatory and hematopoietic responses to chronic hypoxia in two rat strains.

Hilltop (H) and Madison (M) strains of Sprague-Dawley rats exhibit strikingly different susceptibilities to the effects of chronic altitude exposure. The H rats develop greater polycythemia, hypoxemia, and pulmonary hypertension. We studied ventilation, pulmonary gas exchange, tissue oxygenation, and hematologic adaptations in the two rat strains during a 50-day exposure to a simulated altitude (HA) of 5,500 m (18,000 ft). There were no strain differences among the variables we studied under sea level (SL) conditions. Within the first 14 days of hypoxic exposure, the only significant strain differences were that erythropoietin (EPO) rose much higher and erythroid activity was greater in the H rats, even though arterial Po2 and PCo2 (Pao2 and PaCo2, respectively), renal venous PO2 (Prvo2), and ventilation (VE) were equivalent in the two strains during this time. By day 14 at HA, the H rats had significantly higher erythroid activity, hematocrit (Hct), and EPO levels, significantly lower PaO2 and PrvO2, but equivalent VE and PaCO2. These changes persisted for the remainder of the exposure, except that the Hct continued to rise and the increase was greater in H rats. Despite the greater O2-carrying capacity of H rats in the later stages of hypoxic exposure, PaO2 and PrvO2 were significantly lower in H rats. There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance. We conclude that early in the hypoxic exposure the H rats produce more EPO at apparently equivalent levels of hypoxia, and this is the first step in the pathogenesis of the maladaptation to HA manifest by H rats. We find no consistent evidence that differences in VE contribute to the variable susceptibility to hypoxia in the two rat strains.     

Adaptation to chronic hypobaric hypoxia and sexual hormones

The role of the gonads and their hormones on body weight was studied in rats of both sexes submitted to chronic hypoxia and their controls at sea level atmospheric pressure. Intact rats were exposed to either 4 700 or 6 000 m simulated altitude in a hypopressure chamber. Castrated rats and castrated rats daily injected with either 0.5 mg of testosterone or 20 microgram of estradiol or the vehicle, were exposed to the higher altitude. The rat weight was recorded for a period of at least eight weeks. All groups of hypoxic male animals increased their weight significantly less than the controls at sea level. Also in castrated females and in castrated injected with testosterone or the vehicle the same pattern of weight curves was observed. On the contrary, groups of intact females and castrated females injected with estradiol did not show significant differences between hypoxic and control animals. Only in a group of smaller intact females (50-80 g) the body weight increase was significantly diminished by exposure to either 4 700 or 6 000 m simulated altitude.     

Aromatase activity after a short-course of letrozole administration in adult men at sea level and at high altitude (with or without excessive erythrocytosis)

Men living at high altitudes in Peru compared to sea level counterparts have erythrocytosis (hemoglobin 16-21?g/dl) or excessive erythrocytosis (hemoglobin>21?g/dl). High testosterone (T) levels in men at high altitude (HA) were associated with excessive erythrocytosis. High androgen levels could be due to a low aromatase activity or to an elevated rate of conversion from precursors to testosterone. The aim of this study was to evaluate aromatase activity and rate of conversion from precursors to testosterone before and after administration of the aromatase enzyme inhibitor letrozole (5?mg/day) for a 5-day period to men at HA and at sea level (SL). The response to short term aromatase inhibition was assessed in 30 adult men living at sea level, 31 native men at HA with erythrocytosis (Hb 16-21?g/dl), and 35 men at HA with excessive erythrocytosis (Hb>21?g/dl). Serum hormone levels, estradiol/testosterone, testosterone/androstenedione, and testosterone/dehydroepiandrosterone sulfate (DHEAS) ratios were measured. Men with erythrocytosis had lower basal serum T/androstenedione ratios than men with excessive erythrocytosis at HA and men at sea level. Men at HA with excessive erythrocytosis had higher T/DHEAS ratios than men with erythrocytosis and than those at sea level before and after letrozole administration. After letrozole administration, both groups of men at high altitude (with erythrocytosis or with excessive erythrocytosis) showed lower aromatase activities than those at sea level. In conclusion, higher serum testosterone levels in men with excessive erythrocytosis were associated with an increased rate of conversion from DHEAS to testosterone rather than to a lower aromatase activity.     

低氧脑水肿大鼠脑组织VEGF和AQPs基因及蛋白表达的变化

目的：探讨低氧脑水肿时血管内皮细胞生长因子（VEGF）、水通道蛋白（AQP1和AQP4）基因和蛋白表达变化,为阐明急性低氧对脑组织的损伤及低氧脑水肿的发病机制提供实验依据。方法：Wistar大鼠随机分为4个组：常氧对照组（Control）、低氧暴露4 000 m组（4 000 m）、低氧暴露6 000 m组（6 000 m）和低氧暴露8 000 m组（8 000 m）,低氧组于低压舱中模拟相应海拔高度持续暴露8 h建立低氧脑水肿模型。用干-湿重法测定脑组织水含量,常规光镜观察脑组织形态学的改变;用RT-PCR法和免疫组化法检测低氧脑水肿时大鼠脑组织VEGF、AQP1和AQP4mRNA和蛋白表达的变化。结果：①干-湿重法测定表明,低氧（≥6 000 m）暴露后,大鼠脑组织水含量明显增加（P〈0.01）。②常规光镜检测结果表明,低氧暴露4 000 m时大鼠脑神经细胞、血管内皮细胞和星形胶质细胞足突轻度肿胀,组织中出现漏出液;低氧暴露6 000 m时脑血管内皮细胞和星形胶质细胞足突肿胀加重,血管与组织间隙扩大,组织中漏出液增多;低氧暴露8 000m时脑血管内皮细胞和星形胶质细胞足突重度肿胀,血管与组织间隙进一步扩大,组织中漏出液明显增多。③低氧脑水肿时,VEGF、AQP1、AQP4mRNA表达水平增高,AQP1在内皮细胞异常表达,内皮细胞VEGF和AQP1、星形胶质细胞足突AQP4蛋白质表达水平增高。结论：低氧脑水肿时,VEGF、AQP1和AQP4表达和分布的变化可能是引起血脑屏障损伤、导致低氧脑水肿的发病机制之一。     

山西庞泉沟银露梅群落物种多样性的海拔格局

采用样地调查的方法, 对山西庞泉沟银露梅(Potentilla glabra)群落的结构特征、物种多样性随海拔梯度的变化以及沿海拔梯度群落的相似性进行了研究, 并通过R语言对群落α多样性指数间的相关性进行了分析。结果表明: (1) 银露梅群落各层的α多样性指数除生态优势度指数(D)沿海拔梯度的变化不明显外, 其它各指数的变化基本一致。银露梅群落在海拔 1 700-1 900 m与2 100-2 300 m区间内, 灌木层和草本层的α多样性指数均较高, 在海拔1 900-2 000 m区间则较低。另外, 银露梅群落各α多样性指数间除J₂外均呈显著正相关。(2) 随着海拔间隔的增加, 灌木层和草本层的4个β多样性指数的变化均呈上升趋势, 并且草本层随海拔间隔的增加β多样性指数整体比灌木层高。(3) 银露梅群落Jaccard相似性指数随着海拔间隔的增大逐渐减小, 而当海拔达到2 300 m以上时, 群落间的相似性升高, 群落相对稳定。     

郭岩山不同海拔丝栗栲细根功能性状及其与土壤因子的关系

为揭示丝栗栲(Castanopsis fargesii)细根功能性状对环境变化的适应机制,对郭岩山500、700、900 m海拔处丝栗栲细根功能性状及其与土壤因子的关系进行研究。结果表明,丝栗栲细根生物量与细根根长密度、表面积密度、组织密度及体积密度呈正相关,细根根长密度、体积密度、表面积密度和比根长4个性状间均呈极显著正相关关系,且均与细根组织密度呈显著负相关。根际土含水量、C和N含量与细根比根长、根长密度、体积密度、表面积密度均存在显著正相关关系,而土壤容重与细根组织密度呈正相关。海拔700 m的细根生物量、根长密度、表面积密度及体积密度显著大于海拔500和900 m的。500和900 m海拔的根长密度、表面积密度与土壤深度呈负相关,而500 m海拔细根的组织密度与土壤深度呈正相关。因此,郭岩山丝栗栲通过改变细根功能性状来适应海拔和土壤的变化。     

Hemoglobin levels in persons of tibetan ancestry living at high altitude.

The mean hemoglobin level of persons of Tibetan ancestry living at 4000 m in the Nepal Himalayas was found similar to that expected at an altitude of 2300 m and an arterial O2 saturation of 92%. Plasma volumes were normal, and deficiency states and hemoglobinopathies were not significant. Possible reasons for this finding are discussed.     

Glucoregulatory hormones in man at high altitude

Concentrations of glucose, lactic acid, free fatty acid (FFA), insulin, cortisol and growth hormone (GH) in the blood were monitored in 15 euglycaemic men (sojourners, SJ) at sea level (SL) and while at altitudes of 3500 m and 5080 m, in acclimatised low landers (ALL) and in high altitude natives (HAN). In SJ, blood glucose and insulin concentrations showed a significant increase on the 3rd and 7th day after arrival at high altitude (HA), thereafter returning to sea level values and remaining the same during the entire period of their stay at 3500 m. Subsequently, on arrival at higher altitude (5080 m) the glucose concentrations again showed an increase over the preceding values and returned to SL values on day 41 while at 5080 m. A significant increase in cortisol concentrations was seen on day 3 after arrival at HA and the increased levels were maintained until day 21 at 3500 m. The cortisol concentrations on day 30 after arrival at 5080 m came down to SL values and remained unchanged thereafter. No appreciable change in GH and FFA was seen during the sojourn at HA. On the other hand, blood lactic acid concentration decreased significantly. There was no difference between the fasting glucose concentrations in ALL at 3500 m and in HAN at 3500 m and 4200 m compared to values of SJ at SL, whereas ALL at 4200 m had higher glucose values. Concentrations of plasma insulin and GH in ALL and HAN were higher than the values of SJ at SL, whereas cortisol values did not show any difference. These observations indicated that at HA the glucose values were high for the insulin concentration observed and might have been due to increased secretion of GH by the pituitary gland.     

Body composition in air and road inductees at high altitude during the initial days of acclimatization

 This study assesses body composition changes and their time course during the initial days of acclimatization to high altitude (HA). Comparisons were made between gradual and acute induction to HA using 60 male lowlander volunteers (24–28 years of age) divided into two equal groups for inducting them to HA. Thirty subjects were air-lifted from sea level (SL) to 3500 m HA in 1 h. These subjects were air inductees (AI). The other 30 subjects were transported in 4 days by road to the same location at 3500 m. These were road inductees (RI). After remaining for 15 days at 3500 m both groups were inducted to 4200 m by road. All the subjects could not reach the various altitudes at the same time due to logistical problems. Ultimately, data for each altitude (SL, 3500 m and 4200 m) were available for only 26 RI subjects and 10 AI subjects. Skinfold thickness (SKF) measurements for the subscapular, thigh, triceps, biceps, juxtanipple, umbilicus, suprailiac and calf regions were taken in order to calculate fat percentages. Measurements were taken at SL and on days 1 and 9 at both 3500 m and 4200 m. On day 1 at 3500 m, RI showed a significant fall in body weight (BW) with respect to SL but AI maintained it. On subsequent days at HA both groups showed a significant fall in BW and lean body mass but not in percentage fat. SKF in the biceps and triceps regions decreased significantly but in the umbilicus and suprailiac regions it significantly increased at HA in both groups. Body composition, along with other parameters, is discussed determining the acclimatization schedule for sojourners at HA. Possibly, translocation of body fat takes place from the periphery to deep body fat depots in the core/main trunk due to the cold at HA. Received: 8 May 1997 / Revised: 10 August 1997 / Accepted: 20 October 1997     

A randomly-controlled study on the cardiac function at the early stage of return to the plains after short-term exposure to high altitude

High altitude acclimatization and adaptation mechanisms have been well clarified, however, high altitude de-adaptation mechanism remains unclear. In this study, we conducted a controlled study on cardiac functions in 96 healthy young male who rapidly entered the high altitude (3700 m) and returned to the plains (1500 m) after 50 days. Ninety eight healthy male who remained at low altitude were recruited as control group. The mean pulmonary arterial pressure (mPAP), left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), cardiac function index (Tei index) were tested. Levels of serum creatine kinase isoform MB (CK-MB), lactate dehydrogenase isoenzyme-1 (LDH-1), endothelin-1 (ET-1), nitrogen oxide (NO), serum hypoxia-inducible factor-1α (HIF-1α), 8-iso-prostaglandin F(2α) (8-iso PGF(2α)), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at an altitude of 3700 m and 1500 m respectively. The results showed that after short-term exposure to high altitude mPAP and Tei index increased significantly, while LVEF and LVFS decreased significantly. These changes were positively correlated with altitude. On the 15(th) day after the subjects returned to low altitude, mPAP, LVEF and LVFS levels returned to the same level as those of the control subjects, but the Tei index in the returned subjects was still significantly higher than that in the control subjects (P<0.01). We also found that changes in Tei index was positively correlated with mPAP, ET-1, HIF-1α and 8-iso PGF(2α) levels, and negatively correlated with the level of NO, LVEF, LVFS, CK-MB and LDH-1. These findings suggest that cardiac function de-adapts when returning to the plains after short-term exposure to high altitude and the function recovery takes a relatively long time.     

核因子E2相关因子2基因在低氧运动下的表达及其对机体抗氧化能力的调节作用

核因子E2相关因子2 (nuclear factor E2 related factor 2,Nrf2)基因可调节多种抗氧化酶活性并间接影响抗疲劳和抗氧化能力,而低氧环境有助于运动能力的提升。为了考察低氧运动对Nrf2基因敲除小鼠的抗疲劳和抗氧化能力的影响,本研究将敲除Nrf2基因的小鼠置于模拟海拔3 000 m和5 000 m (氧浓度约为14.4%和11.1%)的环境中进行4周的低氧训练。研究发现,模拟海拔3 000 m的低氧运动显著提高了小鼠的力竭跑台运动时间,并减弱了骨骼肌损伤。而模拟海拔5 000 m的低氧运动未出现上述效果。低氧运动显著上调了Nrf2 mRNA表达以及HIF-1α、SOD1、SOD2、GR、GSH-PX、NQO-1和HO-1蛋白表达。模拟海拔3 000 m的低氧运动降低了机体ROS和MDA水平,而模拟海拔5 000 m的低氧运动提高了机体ROS和MDA水平。本研究表明敲除Nrf2抑制了小鼠体内抗氧化酶活性,并降低了小鼠的身体机能。而适当的低氧运动则可通过上调Nrf2和HIF-1α的表达来间接提高抗氧化酶活性,改善机体的氧化-还原状态,从而提高抗疲劳和抗氧化能力。然而,氧浓度过低则会产生相反的效果。     

云南哀牢山地区蕨类植物区系的垂直分布格局

根据大尺度的物种分布信息,利用聚类分析和数理统计的方法分析了云南哀牢山蕨类植物区系的垂直分布格局。研究结果表明,随着海拔的升高,热带区系成分所占比重呈显著递减趋势,而温带区系成分所占比重呈明显递增趋势。在整个海拔梯度上,东亚分布和热带亚洲分布成分始终占主导地位。区系过渡性随着海拔的升高呈先增强后减弱的单峰分布格局,平衡点出现于海拔1700 m左右。基于区系成分比重的聚类分析表明,在海拔1300 m,1900 m和2600 m左右,将海拔梯度上的蕨类植物分为4组,这与各海拔段内的物种组成和区系成分性质是一致的。     

库车种子植物区系垂直分布格局分析

该研究通过野外植被调查及相关文献资料查阅,探讨了库车山区种子植物区系的垂直分布格局特征及其对海拔变化的响应。结果表明:该区种子植物约有78科376属960种。其中,裸子植物3科3属9种,被子植物75科373属951种。植物科、属、种总数随着海拔的升高呈现先增加后降低的单峰分布结构。其中科总数在海拔1 600~1 800 m处为最高峰,属总数在海拔1 800~1 900 m处呈现最高峰;物种总数在海拔1 900~2 000 m处呈现最高峰,有478种(隶属59科,230属)。种子植物区系地理成分分析中,库车山区植物区系垂直海拔梯度上不管是科级水平还是属级水平种类成分都以温带分布型占优势。在垂直分布梯度上,温带分布科最高点出现在海拔1 800~1 900 m(含20科),从海拔2 800~2 900 m开始,随着海拔梯度升高呈现下降趋势,到海拔3 600~3 700 m时为最低点(含6科);温带分布属峰值出现在海拔1 900~2 000 m,随着海拔的升高呈现下降趋势。该研究结果对该区植物种质资源和生态系统多样性,植物资源的引种驯化、栽培和合理利用具有重要意义。     

库车种子植物区系垂直分布格局分析北大核心CSCD

Kuche is located in the middle of the Tianshan Mountains in Xinjiang,the northern margin of the Tarim Basin. In terms of geographical division, the vegetation in this region belongs to the warm temperate shrub and subshrub desert area of Xinjiang. Based on field studies and relevant literature, the vertical distribution characteristics of the flora in Kuche were systematically analyzed. The results showed that there were approximately 960 species of seed plants belonging to 78 families and 376 genera in Kuche. Among these, there were nine species of Gymnosperm belonging to three families and three genera. There were 951 species of Angiosperm belonging to 75 families and 373 genara. The total number of families indicated that the highest peak at the elevation with 1 600-1 800 m. The total number of genera indicated that the highest peak at the elevation with 1 800-1 900 m. The total number of species showed that the highest peak at the elevation with 1 900-2 000 m, there were 59 families, 230 genera, 478 species. From the altitude with 2 200-2 300 m, the number of seed plants family, genus, species showed a decreasing trend with increasing altitude, and the distribution curve showed an unimodal peak distribution structure. North temperate elements were dominant in family and genera floristic composition. In vertical gradients, a peak of temperate distribution type appeared in 1 800-1 900 m(including 20 families), from the altitude gradient with 2 800-2 900 m showed a decreasing trend, to 3 600-3 700 m was the lowest(including six families); The temperate distribution peak of the genus appeared in 1 900-2 000 m, and then decreased with the increase of altitude. This study is very important for the characteristics of the altitude gradients on the flora of seed plants of Kuche Mountain in the area of plant germplasm resources and ecosystem diversity, and plant resources of domestication, cultivation and utilization. [ABSTRACT FROM AUTHOR]