The Muscular Pulmonary Arteries in People Native to High Altitude*

2015 ◽  
pp. 292-301
Author(s):  
Javier Arias-Stella ◽  
Mario Salda�a
Keyword(s):  
High Altitude ◽  
Pulmonary Arteries

Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia

2007 ◽  
Vol 292 (3) ◽  
pp. L678-L684 ◽  
Author(s):  
Yuansheng Gao ◽  
Ada D. Portugal ◽  
Sewite Negash ◽  
Weilin Zhou ◽  
Lawrence D. Longo ◽  
...  
Keyword(s):  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Regulatory Subunit ◽  
Fourth Generation ◽  
Minor Effect ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Rock Activity

An increase in Rho kinase (ROCK) activity is implicated in chronic hypoxia-induced pulmonary hypertension. In the present study, we determined the role of ROCKs in cGMP-dependent protein kinase (PKG)-mediated pulmonary vasodilation of fetal lambs exposed to chronic hypoxia. Fourth generation pulmonary arteries were isolated from near-term fetuses (∼140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for ∼110 days and from control ewes. In vessels constricted to endothelin-1, 8-bromoguanosine-cGMP (8-Br-cGMP) caused a smaller relaxation in chronically hypoxic (CH) vessels compared with controls. Rp-8-Br-PET-cGMPS, a PKG inhibitor, attenuated relaxation to 8-Br-cGMP in control vessels to a greater extent than in CH vessels. Y-27632, a ROCK inhibitor, significantly potentiated 8-Br-cGMP-induced relaxation of CH vessels and had only a minor effect in control vessels. The expression of PKG was increased but was not accompanied with an increase in the activity of the enzyme in CH vessels. The expression of type II ROCK and activity of ROCKs were increased in CH vessels. The phosphorylation of threonine (Thr)696 and Thr850 of the regulatory subunit MYPT1 of myosin light chain phosphatase was inhibited by 8-Br-cGMP to a lesser extent in CH vessels than in controls. The difference was eliminated by Y-27632. These results suggest that chronic hypoxia in utero attenuates PKG-mediated relaxation in pulmonary arteries, partly due to inhibition of PKG activity and partly due to enhanced ROCK activity. Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850.

Effects of hypoxia on density of beta-adrenergic receptors

1981 ◽  
Vol 50 (2) ◽  
pp. 363-366 ◽  
Author(s):  
N. F. Voelkel ◽  
L. Hegstrand ◽  
J. T. Reeves ◽  
I. F. McMurty ◽  
P. B. Molinoff
Keyword(s):  
High Altitude ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Low Dose ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Altitude Exposure

Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta-adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines.

High Altitude Hypoxia Induces Cellular Immaturity of Pulmonary Arteries in the Fetal Lamb: Assessment of Protein Biomarkers

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Breanna Jones ◽  
Eric Leslie ◽  
Rafael Alvarez ◽  
Chiranjib Dasgupta ◽  
Lubo Zhang ◽  
...  
Keyword(s):  
High Altitude ◽  
Pulmonary Arteries ◽  
Protein Biomarkers ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Fetal Lamb

The Muscular Pulmonary Arteries in People Native to High Altitude

Respiration ◽  
1962 ◽  
Vol 19 (5) ◽  
pp. 484-493 ◽  
Author(s):  
Javier Arias-Stella ◽  
Mario Saldaña
Keyword(s):  
High Altitude ◽  
Pulmonary Arteries

Functional and structural adaptation of the yak pulmonary circulation to residence at high altitude

1993 ◽  
Vol 74 (5) ◽  
pp. 2276-2285 ◽  
Author(s):  
A. G. Durmowicz ◽  
S. Hofmeister ◽  
T. K. Kadyraliev ◽  
A. A. Aldashev ◽  
K. R. Stenmark
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
High Altitude ◽  
Pulmonary Circulation ◽  
Vascular Reactivity ◽  
Cell Function ◽  
Pulmonary Arteries ◽  
Structural Adaptation ◽  
Endothelial Cell Function

The high-altitude (HA) native yak (Bos grunniens) has successfully adapted to chronic hypoxia (CH) despite being in the same genus as domestic cows, which are known for their great hypoxic pulmonary vasoconstrictor responses (HPVRs), muscular pulmonary arteries, and development of severe pulmonary hypertension on exposure to CH. To determine possible mechanisms by which the pulmonary circulation may adapt to CH, yak pulmonary vascular reactivity to both vasoconstrictor and vasodilator stimuli and yak pulmonary artery structure were assessed. Hypoxia caused a small but significant HPVR, and norepinephrine infusion caused a greater rise in pulmonary arterial pressure (Ppa) than did hypoxia. Acetylcholine, an endothelium-dependent vasodilator, had no effect on Ppa but lowered pulmonary resistance (Rp) by causing an increase in cardiac output. Sodium nitroprusside, an endothelium-independent vasodilator, decreased both Ppa and Rp significantly. Yak small pulmonary arteries had a 4.1 +/- 0.1% medial thickness, with vessels < or = 100 microns devoid of smooth muscle. Yak pulmonary artery endothelial cells were much longer, wider, and rounder in appearance than those of domestic cows. Thus the yak has successfully adapted to HA conditions by maintaining both a blunted HPVR and thin-walled pulmonary vessels. Differences in both endothelial cell morphology and response to acetylcholine between the yak and those reported in the domestic cow suggest the adaptation to HA may include changes not only in the amount of pulmonary vascular smooth muscle but in endothelial cell function and structure as well.

scholarly journals Rho/ROCK is Up‐regulated in Pulmonary Arteries of Pregnant Ewes in Chronic High Altitude Hypoxia

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Sewite Negash ◽  
Yuansheng Gao ◽  
Ada M. Portugal ◽  
L.D. Longo ◽  
J. Usha Raj
Keyword(s):  
High Altitude ◽  
Pulmonary Arteries ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia

Comparative analysis of skeleton muscle proteome profile between yak and cattle provides insight into high-altitude adaptation

2020 ◽  
Vol 17 ◽  
Author(s):  
Jin-Wei Xin ◽  
Zhi-Xin Chai ◽  
Cheng-Fu Zhang ◽  
Yu-Mei Yang ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
High Altitude ◽  
Pyruvate Dehydrogenase ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Pyruvate Dehydrogenase Complex ◽  
Pulmonary Arteries ◽  
Adenosine Monophosphate ◽  
Oxygen Utilization ◽  
Antibody Microarray ◽  
Expression Levels

Background:: Mechanisms underlying yak adaptation to high-altitude environments have been investigated at levels of morphology, anatomy, physiology, genome and transcriptome, but not at the proteome level. Objective: To explore for the first time the protein expression profiles in yak to reveal molecular mechanisms underlying adaptation to high altitude, up to now investigated by genome sequencing. Methods: In the present study, an antibody microarray chip was developed, which included 6,500 mouse monoclonal antibodies. Immunoprecipitation and mass spectrometry on 12 selected antibodies showed that the chip was highly specific. Using this chip, muscle tissue proteome was compared between yak and cattle, and 12 significantly differentially expressed proteins (DEPs) were identified and their expression levels were validated by Western blot. Results: Compared with cattle, higher levels of Rieske iron-sulfur protein (RISP), Cytochrome C oxidase subunit 4 isoform 1, mitochondrial (COX4I1), ATP synthase F1 subunit beta (ATP5F1B), Sarcoplasmic/endoplasmic reticulum calcium ATPase1 (SERCA1) and Adenosine monophosphate deaminase1 (AMPD1) in yak might increase oxygen utilization and energy metabolism. Pyruvate dehydrogenase protein X component (PDHX) and Acetyltransferase component of pyruvate dehydrogenase complex (DLAT) showed higher expression levels and L-lactate dehydrogenase A chain (LDHA) showed lower expression level, which might help yak reduce accumulation of lactic acid. In addition, higher expression levels of Filamin C (FLNC) and low levels of AHNAK and Four and a half LIM domains 1(FHL1) in yak might contribute to inhibition of pulmonary arteries vasoconstriction, remodeling and hypertension. Conclusion: Overall, the present study reported new data at protein level in comparison between yak and cattle, which might be helpful to further understand molecular mechanisms underlying yak adaptation to high altitude environments.

Pulmonary hypertension is attenuated and ventilation-perfusion matching is maintained during chronic hypoxia in deer mice native to high altitude

2021 ◽  
Author(s):  
Claire M. West ◽  
Oliver H. Wearing ◽  
Rod G. Rhem ◽  
Graham R. Scott
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Right Ventricle ◽  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Deer Mice ◽  
Maladaptive Response ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Hypoxia at high altitude can constrain metabolism and performance, and can elicit physiological adjustments that are deleterious to health and fitness. Hypoxic pulmonary hypertension is a particularly serious and maladaptive response to chronic hypoxia, which results from vasoconstriction and pathological remodeling of pulmonary arteries, and can lead to pulmonary edema and right ventricle hypertrophy. We investigated whether deer mice (Peromyscus maniculatus) native to high altitude have attenuated this maladaptive response to chronic hypoxia, and whether evolved changes or hypoxia-induced plasticity in pulmonary vasculature might impact ventilation-perfusion (V-Q) matching in chronic hypoxia. Deer mouse populations from both high and low altitudes were born and raised to adulthood in captivity at sea level, and various aspects of lung function were measured before and after exposure to chronic hypoxia (12 kPa O2, simulating the O2 pressure at 4300 m) for 6-8 weeks. In lowlanders, chronic hypoxia increased right ventricle systolic pressure (RVSP) from 14 to 19 mmHg (P = 0.001), in association with thickening of smooth muscle in pulmonary arteries and right ventricle hypertrophy. Chronic hypoxia also impaired V-Q matching in lowlanders (measured at rest using SPECT-CT imaging), as reflected by increased log SD of the perfusion distribution (log SDQ) from 0.55 to 0.86 (P = 0.031). In highlanders, chronic hypoxia had attenuated effects on RVSP and no effects on smooth muscle thickness, right ventricle mass, or V-Q matching. Therefore, evolved changes in lung function help attenuate maladaptive plasticity and contribute to hypoxia tolerance in high-altitude deer mice.

Effect of long-term high-altitude hypoxia on fetal pulmonary vascular contractility

2008 ◽  
Vol 104 (6) ◽  
pp. 1786-1792 ◽  
Author(s):  
Qin Xue ◽  
Charles A. Ducsay ◽  
Lawrence D. Longo ◽  
Lubo Zhang
Keyword(s):  
High Altitude ◽  
Pulmonary Arteries ◽  
Common Mechanism ◽  
Maximal Response ◽  
Pulmonary Vessel ◽  
Altitude Hypoxia ◽  
Protein Levels ◽  
High Altitude Hypoxia ◽  
Increased Risk

Hypoxia in the fetus and/or newborn is associated with an increased risk of pulmonary hypertension. The present study tested the hypothesis that long-term high-altitude hypoxemia differentially regulates contractility of fetal pulmonary arteries (PA) and veins (PV) mediated by differences in endothelial NO synthase (eNOS). PA and PV were isolated from near-term fetuses of pregnant ewes maintained at sea level (300 m) or high altitude of 3,801 m for 110 days (arterial Po2 of 60 Torr). Hypoxia had no effect on the medial wall thickness of pulmonary vessels and did not alter KCl-induced contractions. In PA, hypoxia significantly increased norepinephrine (NE)-induced contractions, which were not affected by eNOS inhibitor NG-nitro-l-arginine (l-NNA). In PV, hypoxia had no effect on NE-induced contractions in the absence of l-NNA. l-NNA significantly increased NE-induced contractions in both control and hypoxic PV. In the presence of l-NNA, NE-induced contractions of PV were significantly decreased in hypoxic lambs compared with normoxic animals. Acetylcholine caused relaxations of PV but not PA, and hypoxia significantly decreased both pD2 and the maximal response of acetylcholine-induced relaxation in PV. Additionally, hypoxia significantly decreased the maximal response of sodium nitroprusside-induced relaxations of both PA and PV. eNOS was detected in the endothelium of both PA and PV, and eNOS protein levels were significantly higher in PV than in PA in normoxic lambs. Hypoxia had no significant effect on eNOS levels in either PA or PV. The results demonstrate heterogeneity of fetal pulmonary arteries and veins in response to long-term high-altitude hypoxia and suggest a likely common mechanism downstream of NO in fetal pulmonary vessel response to chronic hypoxia in utero.

The Small Pulmonary Arteries in Rats at Simulated High Altitude

Pathobiology ◽  
1973 ◽  
Vol 39 (3-4) ◽  
pp. 270-275 ◽  
Author(s):  
J.M. Kay ◽  
P. Smith
Keyword(s):  
High Altitude ◽  
Pulmonary Arteries ◽  
Simulated High Altitude
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