scholarly journals Long-Term High-Altitude Hypoxia and Alpha Adrenoceptor-Dependent Pulmonary Arterial Contractions in Fetal and Adult Sheep

2019 ◽  
Vol 10 ◽  
Author(s):  
Dafne Moretta ◽  
Demosthenes G. Papamatheakis ◽  
Daniel P. Morris ◽  
Paresh C. Giri ◽  
Quintin Blood ◽  
...  
Keyword(s):  
High Altitude ◽  
Altitude Hypoxia ◽  
Adult Sheep ◽  
Alpha Adrenoceptor ◽  
High Altitude Hypoxia ◽  
Pulmonary Arterial

Heme oxygenase activity in fetal and adult sheep is not altered by acclimatization to high altitude hypoxia

2006 ◽  
Vol 84 (8-9) ◽  
pp. 893-901 ◽  
Author(s):  
Robert T. Kinobe ◽  
Jason Z. Vlahakis ◽  
Jonathan M. Soong ◽  
Walter A. Szarek ◽  
James F. Brien ◽  
...  
Keyword(s):  
High Altitude ◽  
Heme Oxygenase ◽  
Stress Proteins ◽  
Degradation Products ◽  
Fetal Tissue ◽  
Altitude Hypoxia ◽  
Adult Sheep ◽  
High Altitude Hypoxia

Hypoxic stress has been reported to induce the expression of stress proteins such as heme oxygenase (HO), which catalyze the breakdown of heme to generate biliverdin, ferrous iron, and carbon monoxide. These degradation products play a role in the regulation of a variety of processes such as vascular tone, inflammation, and central nervous system function. In mammals, there are 2 catalytically functional HO isozymes, HO-1 (inducible) and HO-2 (constitutive). HO-1 expression is regulated by an array of nonphysiological and physiological stimuli including acute hypoxemia. As relatively little is known of the HO response to prolonged hypoxia in whole animals other than small laboratory rodents, the aim of this work was to examine the effect of long-term hypoxia on total HO activity in fetal and adult ovine tissue. Sheep were maintained at high altitude (3820 m), after which the following tissues were harvested from near-term fetal and non-pregnant ewes for in vitro measurement of HO activity: left ventricle, renal papilla, lung apex, pulmonary artery, carotid artery, mesenteric artery, placental cotyledon, spleen, and brain frontal cortex. There were no significant differences between HO activities in tissues from hypoxic fetal and adult sheep compared with their normoxic controls. Fetal heart HO activities were higher than those of adult tissue (p < 0.05), whereas adult spleen HO activity was significantly higher than that of fetal tissue (p < 0.05). In conclusion, these data indicate that long-term exposure to high altitude hypoxia does not have a persistent effect on HO activity in ovine tissues. Also, except for the spleen where there is a high expression of HO-1 under normal conditions, tissue HO activity is correlated with the expression of HO-2, the constitutive isozyme.

scholarly journals Preservation of Serotonin-Mediated Contractility in Adult Sheep Pulmonary Arteries Following Long-Term High-Altitude Hypoxia

2011 ◽  
Vol 12 (3) ◽  
pp. 253-264 ◽  
Author(s):  
Demosthenes G. Papamatheakis ◽  
Srilakshmi Vemulakonda ◽  
Quintin Blood ◽  
Ravi Goyal ◽  
Monica Rubalcava ◽  
...  
Keyword(s):  
High Altitude ◽  
Pulmonary Arteries ◽  
Altitude Hypoxia ◽  
Adult Sheep ◽  
High Altitude Hypoxia

Ca2+ Sensitivity of Fetal Coronary Arteries Exposed to Long-Term, High-Altitude Hypoxia

2000 ◽  
Vol 7 (3) ◽  
pp. 161-166 ◽  
Author(s):  
Felizabel C. Garcia ◽  
Virginia M. Stiffel ◽  
William J. Pearce ◽  
Lubo Zhang ◽  
Raymond D. Gilbert
Keyword(s):  
High Altitude ◽  
Coronary Arteries ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia

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.

Chronic hypoxia alters the function of NOS nerves in cerebral arteries of near-term fetal and adult sheep

2003 ◽  
Vol 94 (2) ◽  
pp. 724-732 ◽  
Author(s):  
Emmanuel M. Mbaku ◽  
Lubo Zhang ◽  
William J. Pearce ◽  
Sue P. Duckles ◽  
John Buchholz
Keyword(s):  
Nitric Oxide ◽  
Electrical Stimulation ◽  
High Altitude ◽  
Cerebral Arteries ◽  
Nerve Function ◽  
Altitude Hypoxia ◽  
Adult Sheep ◽  
High Altitude Hypoxia ◽  
No Release ◽  
Near Term

In addition to adrenergic innervation, cerebral arteries also contain neuronal nitric oxide synthase (nNOS)-expressing nerves that augment adrenergic nerve function. We examined the impact of development and chronic high-altitude hypoxia (3,820 m) on nNOS nerve function in near-term fetal and adult sheep middle cerebral arteries (MCA). Electrical stimulation-evoked release of norepinephrine (NE) was measured with HPLC and electrochemical detection, whereas nitric oxide (NO) release was measured by chemiluminescence. An inhibitor of NO synthase, N ω-nitro-l-arginine methyl ester (l-NAME), significantly inhibited stimulation-evoked NE release in MCA from normoxic fetal and adult sheep with no effect in MCA from hypoxic animals. Addition of the NO donor S-nitroso- N-acetyl-dl-penicillamine fully reversed the effect of l-NAME in MCA from normoxic animals with no effect in MCA from hypoxic animals. Electrical stimulation caused a significant increase in NO release in MCA from normoxic animals, an effect that was blocked by the neurotoxin tetrodotoxin, whereas there was no increase in NO release in MCA from hypoxic animals. Relative abundance of nNOS as measured by Western blot analysis was similar in normoxic fetal and adult MCA. However, after hypoxic acclimitization, nNOS levels dramatically declined in both fetal and adult MCA. These data suggest that the function of nNOS nerves declines during chronic high-altitude hypoxia, a functional change that may be related to a decline in nNOS protein levels.

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