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PubMed1983

[Capillary filtration coefficient and the distensibility of the venous vessels of the small intestine in the process of high-altitude adaptation].

In acute experiments on cats, the increase of capillary filtration coefficient and venous distensibility in small intestine was revealed after 3-5, 14-16 and 29-31 days of high altitude adaptation (The Pamirs, 3370 m above sea level), the changes being more obvious (by 78% and 45%, resp.) after 3-5 days in comparison with low altitude control. The effects of noradrenaline on the small intestine precapillary sphincters and venous distensibility were preserved at high altitude, whereas regional blockade of alpha- or beta-adrenoreceptors exerted no effect on the results. The increased capillary filtration coefficient seems to be of great importance in "struggle for oxygen" at high altitude hypoxia, and this obviously depends on the opening of preexisting capillaries.

Adaptation, Physiological↗
PubMed1984

High-altitude adaptation and maximum work performance.

The treadmill work performance of rats at sea level with normal or elevated hematocrits was compared with that of rats conditioned in a hypobaric chamber at 450 Torr for 3 wk with similar hematocrit adjustments. A mean increase in hematocrit to 62 significantly improved the work performance of rats at sea level and at ambient O2 tensions of 100, 75, and 35 Torr. By contrast, rats conditioned in a hypobaric chamber with mean hematocrits of 40 and 58 performed similarly at all O2 tensions compared with sea-level rats with hematocrits of 43. Thus, although an increase in O2-carrying capacity of the blood of sea-level animals increased work capacity, altitude adaptation did not appear to result in any positive effect on work capacity, and indeed, seemed to interfere with the beneficial effect of polycythemia on maximum work performance.

Adaptation, Physiological↗
PubMed2026

Identifying causal genetic variants for high-altitude adaptation through blood eQTL analysis in plateau populations.

A substantial number of genetic variants have been associated with high-altitude adaptation (HAA), yet most of them are located in non-coding genomic regions, leaving their specific functions and underlying mechanisms largely unknown. In this study, we analyze whole-genome and transcriptome sequencing data from a self-established cohort comprising 61 native highlanders (NHs) and 164 acclimatized newcomers (ANs), identifying 6,586 cis- and 34,203 trans-expression quantitative trait loci (eQTLs), along with 130 cell type-specific eQTLs. By further combining these data with a large East Asia (~30% Tibetan) genome-wide association study (GWAS) cohort, we employ colocalization and causal inference analyses to prioritize 85 cis-eQTLs associated with HAA and identify several novel candidate causal genes, including EXOC8, which is experimentally confirmed to regulate erythroid differentiation. Additionally, network analysis of these causal genes uncovers multiple regulatory pathways, mainly involving energy metabolism, autophagy, ubiquitination and inflammation. Our study offers a comprehensive eQTL map and reveals causal chains of "variant-gene-phenotype" for HAA-related traits, which provides new insights into potential regulatory mechanisms and targets for prevention and treatment of altitude sickness.

Quantitative Trait Loci↗
PubMed2026

Comparative analysis of olfactory receptor repertoires reveals evolutionary dynamics and high-altitude adaptation in Schizopygopsis younghusbandi based on the chromosome-level genomes.

The olfactory receptor (OR) gene represent a significant multigene family in vertebrates, forming the core molecular basis of olfactory perception and playing a crucial role in the environmental adaptation of species. High-altitude ecosystems represent extreme habitats characterized by specific abiotic stresses, including low oxygen levels, low temperatures, and intense ultraviolet radiation. These environments also exhibit low aquatic biodiversity and a limited variety of odor molecules, factors that have influenced the adaptive evolution of the sensory systems in endemic species. However, the genetic mechanisms underlying olfactory adaptation in high-altitude freshwater fish remained inadequately understood. In this study, we performed comparative genomics analyses to reveal the evolutionary processes underlying the adaptive and functional evolution of OR genes in S. younghusbandi, a cyprinid fish endemic to the Qinghai-Xizang Plateau. The results indicated that, compared to their low-altitude relatives, S. younghusbandi possessed a significantly smaller number of OR genes, with only 98 genes, which revealed the contraction of the gene family. Phylogenetic analysis revealed that the OR genes of cyprinid fish could be categorized into two major lineages: type I and type II. The η and δ families, which perceive water-soluble odors, in S. younghusbandi underwent significant and specific expansion, while the ε family was completely absent. This pattern reflected adaptive changes in olfactory recognition to accommodate the simplified odor spectrum of high-altitude water bodies. Chromosomal localization analysis demonstrated that OR genes were clustered, and collinearity analysis confirmed the presence of conserved genomic fragments among species. Selection pressure analysis revealed that the Ka/Ks values of all homologous gene pairs were less than 1, indicating that the OR genes of S. younghusbandi underwent strong purifying selection as a group to preserve core olfactory function. A few genes exhibited relaxed selection characteristics, which may have facilitated the fine-tuning of adaptability to high-altitude environments. In conclusion, this study elucidated the evolutionary dynamics and adaptive characteristics of the OR gene in S. younghusbandi, offering a new perspective on the molecular mechanisms underlying olfactory adaptation at high altitudes and enriching the research on sensory evolution in vertebrates.

Schizopygopsis younghusbandi↗
PubMed1983

[Interaction of the heart ventricles in intact dogs on the 3rd to 5th day of high-altitude adaptation].

Cardiac output studied on the 3rd-5th days of adaptation to 3200 m altitude in dogs born at the 760 m and 1800 m altitudes revealed that the adaptation led to the right ventricle hyperfunction in former group of dogs whereas in the latter group of dogs it was followed by the left ventricle hyperfunction with higher end-diastolic pressure in both ventricles, at that. It seems that when the balance of the ventricles is mechanically disturbed, hyperfunction of one heart's part leads to dysfunction of the opposite part.

Acclimatization↗
PubMed2003

Cardiopulmonary hemodynamics of blue-sheep, Pseudois nayaur, as high-altitude adapted mammals.

The blue-sheep, pika, and yak live in the Tibetan highlands at an altitude of 6,100 m and are typical mammals adapted to high-altitudes. These animals have a long history of habitation at high-altitudes and are considered to be "animals completely adapted to high-altitudes" because of their physiological and morphological traits that are well adapted to high-altitude environments. To evaluate the physiological characteristics of high-altitude adaptation in the blue-sheep, changes in the pulmonary hemodynamics during exposure to simulated-altitudes at 0, 2,300, and 4,500 m were examined by means of a climatic chamber in Qinghai Province, China (altitude 2,300 m). Seven blue-sheep inhabiting the mountains (3,000 m) of Qinghai Province, China, were compared with 5 pigs raised in the same area as controls. The primary items of measurement were the body weight (BW), systemic arterial pressure (Psa), pulmonary artery pressure (Ppa), hematocrit (Ht), left ventricular weight (LVW), right ventricular weight (RVW), and blood gas profile. The principal findings of this study are: (1) Ht, an index of right ventricular hypertrophy (RVW/LVW), and oxygen consumption (Vdot;O(2)) were significantly lower in the blue sheep compared with the pigs; (2) When the animals were exposed to simulated-altitudes at 0, 2,300, and 4,500 m, Ppa increased significantly in tandem with altitude elevation in both species, but the increases were significantly smaller in the blue-sheep; and (3) Ppa/Psa, an index of the right ventricular load, increased with the altitude in both species, but the increases were smaller in the blue sheep. From these observations, low Ht and RVW/LVW and significant attenuation of hypoxic pulmonary vasoconstriction (HPV) in the blue-sheep is considered to be characteristics of animals completely adapted to high-altitudes, such as the pika.

Altitude↗
PubMed2001

Angiotensin converting enzyme insertion allele in relation to high altitude adaptation.

Angiotensin converting enzyme (ACE) gene I/D polymorphism has been associated with high altitude (HA) disorders as well as physical performance. We, however, envisage that the polymorphism may be associated with adaptation to the hypobaric hypoxia of altitude, thus facilitating physical performance. For this purpose, three unrelated adult male groups, namely (1) the Ladakhis (HLs), who reside at and above a height of 3600 m, (2) lowlanders, who migrated to Ladakh (MLLs), and (3) resident lowlanders (LLs), have been investigated. The HLs had significantly (p & 0.001) greater numbers of the II homozygotes and the ID heterozygotes than the DD homozygotes, the genotype distribution being 0.46, 0.43 and 0.11 for II, ID and DD genotypes respectively. The MLLs comprised 60% II homozygotes, which was higher (p & 0.001) than the HLs (46%). In the LLs, the heterozygotes were greater (p & 0.001) in number than the II and DD homozygotes. The I allele frequency was 0.72 in the MLLs, 0.67 in the HLs and 0.55 in the LLs. Polymorphism study suggested that the II genotype could be associated with altitude adaptation, which might influence physical efficiency.

Adaptation, Physiological↗
PubMed1983

[Thermogenic responses of high-altitude adapted rats on low temperatures and low pressures].

The male rats were raised in two groups, one at Mt. Yatsugatake (2,100 m above sea level, the average ambient temperature 12.5 degrees C) for 30 days, and the other at a laboratory of Matsumoto (610 m above sea level, the average temperature 20 degrees C). The steady-state oxygen consumptions (VO2) and the rectal temperatures (TR) were measured under exposure conditions of various temperatures combined with different simulated altitudes. The values of VO2 and TR for a control group at 610 m-20 degrees C were regarded as 100% and the relative changes to the control values were obtained at various temperatures in the respective low-pressure condition. When measured at a simulated altitude of 2,000 m on the 2nd day after the rats raised at Mt. Yatsugatake were translocated to Matsumoto, the values at 0 degrees C and 10 degrees C room temperatures, VO2 and TR, were still significantly increased as compared with those of rats raised at Matsumoto. On the 40th day after the translocation from Mt. Yatsugatake, however, the values turned out to exhibit no significant difference in both groups. These results indicated that the greater thermogenesis of high-altitude adapted rats had been established by combined stimuli of low temperatures and low pressures as compared with those of Matsumoto-level adapted rats, but the responses returned to the control level by deadaptation process at 40 days after the translocation.

Acclimatization↗
PubMed2002

Novel mechanism for high-altitude adaptation in hemoglobin of the Andean frog Telmatobius peruvianus.

In contrast to birds and mammals, no information appears to be available on the molecular adaptations for O(2) transport in high-altitude ectothermic vertebrates. We investigated Hb of the aquatic Andean frog Telmatobius peruvianus from 3,800-m altitude as regards isoform differentiation, sensitivity to allosteric cofactors, and primary structures of the alpha- and beta-chains, and we carried out comparative O(2)-binding measurements on Hb of lowland Xenopus laevis. The three T. peruvianus isoHbs show similar functional properties. The high O(2) affinity of the major component results from an almost complete obliteration of chloride sensitivity, which correlates with two alpha-chain modifications: blockage of the NH(2)-terminal residues and replacement by nonpolar Ala of polar residues Ser and Thr found at position alpha131(H14) in human and X. leavis Hbs, respectively. The data indicate adaptive significance of alpha-chain chloride-binding sites in amphibians, in contrast to human Hb where chloride appears mainly to bind in the cavity between the beta-chains. The findings are discussed in relation to other strategies for high-altitude adaptations in amphibians.

Adaptation, Physiological↗
PubMed2004

Endogenous nitric oxide and pulmonary circulation response to hypoxia in high-altitude adapted Tibetan sheep.

Nitric oxide (NO) is important for the pulmonary circulation response to acute and chronic hypoxia. We examined effects of endogenous nitric oxide synthase (NOS) inhibition on pulmonary vascular tone in response to hypoxia in Tibetan sheep dwelling at 3,000 m above sea level using a pressure chamber. Unanaesthetized male sheep living at 2,300 m above sea level ( n=7) were prepared for vascular monitoring. Pulmonary artery ( P(pa)), pulmonary artery wedge ( P(cwp)) and systemic artery pressures together with cardiac output (CO) were measured, and pulmonary vascular resistance (PVR) was calculated as ( P(pa)- P(cwp))/CO. A non-selective NOS inhibitor, N(omega)-nitro- l-arginine (NLA; 20 mg kg(-1)), and a selective NOS inhibitor, ONO-1714 (0.1 mg kg(-1)), were used and measurements were made at 0 m, 2,300 m, and 4,500 m, with and without the NOS inhibitors. After NLA, P(pa) increased slightly and CO decreased in animals at baseline (2,300 m). The increased PVR after NLA at 4,500 m was greater than that at 2,300 m ( P<0.05). Selective NOS inhibition increased PVR at baseline, but not at 4,500 m. The enhanced pulmonary vasoconstriction after NO inhibition at basal and hypoxic conditions suggests a modulating role of NOS bioactivity in the pulmonary circulation and that augmented endothelial NOS plays a counterregulatory role in the pulmonary vasoconstrictor response to acute hypoxia in high-altitude adapted Tibetan sheep.

Acclimatization↗
PubMed2005

Simultaneous selection of the wild-type genotypes of the G894T and 4B/ 4A polymorphisms of NOS3 associate with high-altitude adaptation.

The routine performance of high-altitude (HA) natives in the hypoxic environment of HA exemplifies the process of adaptation mainly through natural selection. The recent therapeutic application of nitric oxide (NO) in HA disorders, for the improvement of oxygenation and vasodilation, ushered us to investigate the endothelial nitric oxide synthase gene (NOS3) with respect to HA adaptation. The study subjects, 131 HA monks (HAM), 136 HA controls (HAC), and 170 lowlanders (LLs) were screened for NOS3 G894T (Glu298Asp) and 4B/4A polymorphisms. The NO levels were estimated, for a correlation with the polymorphisms. The three groups were in Hardy-Weinberg equilibrium for the polymorphisms. The overall genotype distributions for the G894T and 4B/4A polymorphisms were significant (P = 0.01 and 0.02, respectively) in the three groups. Wild-type alleles G and 4B were significantly over-represented in the HA groups as compared to the LLs (P = 0.006 and P = 0.02, respectively). The NO levels were in the order of HAM>HAC>LLs (P < 0.0001). Furthermore, combinations of the GG and BB genotypes were distributed significantly more frequently in the HAM (P < 0.0001) and HAC (P = 0.0005) than in LLs. The NO levels contributed by the wild-type genotype combination GG, BB were significantly elevated when compared with the remaining eight genotype combinations together in the HAM, HAC and LLs (P = 0.003, P = 0.0006 and P < 0.0001, respectively). To conclude, the genotype combination of NOS3 wild-type homozygotes (GG, BB) was found significantly more frequently in HA groups than in LLs, by contributing to higher NO levels associated with HA adaptation.

Adaptation, Physiological↗
PubMed1987

Substrate and O2 fluxes during rest and exercise in a high-altitude-adapted animal, the llama.

Llamas were trained to exercise on a treadmill at graded speeds. O2 uptake values at rest, at modest exercise (ME, 0.58 m/s), and at heavy exercise (HE, 1.84 m/s) were 0.069, 0.297, and 0.594 ml O2 X kg-1 X s-1. Corresponding values for cardiac output were 1.64, 4.39, and 6.85 ml X kg-1 X s-1. Palmitate, glucose, and lactate replacement rates (Ra values) were determined at these varying work rates using a single-bolus injection of 14C- or 3H-labeled metabolites, two at a time. Ra values for palmitate, glucose, and lactate at rest were 6.2, 61.4, and 36.1 mumol X kg-1 X min-1, respectively. During ME, the Ra values for glucose and palmitate increased about twofold but showed no further increase when exercise intensity was increased about twofold. In contrast to these results, Ra values for lactate increased much more with increasing work rate. A combination of increased perfusion (increased cardiac output) and increased lactate availability (increased plasma concentration) could account for the lactate Ra data. During prolonged ME, the Ra for lactate decreased because lactate availability decreased; concurrently, both the plasma free fatty acid availability and the Ra values for palmitate greatly increased. Because O2 carrying capacity is low in the llama (as in all high-altitude-adapted mammals), a given level of exercise required exaggerated increases in cardiac output (and hence in perfusion rates of working muscles). As a result, the flux rates of palmitate, glucose, and lactate through the plasma compartment could readily account for O2 flux rates even at relatively high sustainable rates of exercise.

Acclimatization↗