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.

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

scholarly journals Blunted nitric oxide regulation in Tibetans under high-altitude hypoxia

2018 ◽  
Vol 5 (4) ◽  
pp. 516-529 ◽  
Author(s):  
Yaoxi He ◽  
Xuebin Qi ◽  
Ouzhuluobu ◽  
Shiming Liu ◽  
Jun Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
High Altitude ◽  
Gene Knockout ◽  
Umbilical Vein ◽  
Adaptive Strategy ◽  
Han Chinese ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Gene Knockout Mice ◽  
No Signaling

ABSTRACT Nitric oxide (NO) is an important molecule for vasomotor tone, and elevated NO signaling was previously hypothesized as a unique and adaptive physiological change in highland Tibetans. However, there has been lack of NO data from Tibetans living at low altitude and lowlander immigrants living at high altitude, which is crucial to test this hypothesis. Here, through cross-altitude (1990–5018 m) and cross-population (Tibetans and Han Chinese) analyses of serum NO metabolites (NOx) of 2086 individuals, we demonstrate that although Tibetans have a higher serum NOx level compared to lowlanders, Han Chinese immigrants living at high altitude show an even higher level than Tibetans. Consequently, our data contradict the previous proposal of increased NO signaling as the unique adaptive strategy in Tibetans. Instead, Tibetans have a relatively lower circulating NOx level at high altitude. This observation is further supported by data from the hypoxic experiments using human umbilical vein endothelial cells and gene knockout mice. No difference is detected between Tibetans and Han Chinese for endothelial nitric oxide synthase (eNOS), the key enzyme for circulating NO synthesis, suggesting that eNOS itself is unlikely to be the cause. We show that other NO synthesis-related genes (e.g. GCH1) carry Tibetan-enriched mutations significantly associated with the level of circulating NOx in Tibetans. Furthermore, gene network analysis revealed that the downregulation and upregulation of NOx is possibly achieved through distinct pathways. Collectively, our findings provide novel insights into the physiological and genetic mechanisms of the evolutionary adaptation of Tibetans to high-altitude hypoxia.

Nitric Oxide Levels and Adaptation to High Altitude Hypoxia

2010 ◽  
Vol 49 ◽  
pp. S12
Author(s):  
Serpil Erzurum ◽  
Martin Feelisch ◽  
Cynthia Beall
Keyword(s):  
Nitric Oxide ◽  
High Altitude ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia

scholarly journals Ins(1,4,5)P3 receptors in cerebral arteries: changes with development and high-altitude hypoxia

1997 ◽  
Vol 272 (6) ◽  
pp. R1954-R1959 ◽  
Author(s):  
L. Zhou ◽  
Y. Zhao ◽  
R. Nijland ◽  
L. Zhang ◽  
L. D. Longo
Keyword(s):  
High Altitude ◽  
Cerebral Arteries ◽  
Age Groups ◽  
Receptor Density ◽  
Altitude Hypoxia ◽  
Contractile Responses ◽  
Adult Sheep ◽  
Developmental Age ◽  
Density Values

We and others have shown that adrenergic-mediated contractile responses in cerebral vessels in vitro differ with vessel segment, with developmental age, and with high-altitude, long-term hypoxia. This is associated with significant differences in alpha 1-adrenergic receptor density and norepinephrine (NE)-induced response of the second messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. To test the hypothesis that vessel-specific, developmental, and hypoxic-associated contractility changes are mediated, in part, by changes in Ins(1,4,5)P3-receptor [Ins(1,4,5)P3-R] density or affinity, we performed the following study. In common carotid (Com), circle of Willis, and main branch anterior, middle, and posterior cerebral arteries (MBC) from normoxic fetal (approximately 140 days), newborn (3-5 days), and adult sheep and fetal and adult sheep acclimatized to high altitude, we quantified Ins(1,4,5)P3-R with [3H]Ins(1,4,5)P3. In normoxic Com, Ins(1,4,5)P3-R density values (fmol/mg protein) in fetus, newborn, and adult were 8 +/- 53, 150 +/- 18, and 357 +/- 21, respectively (P < 0.05). In normoxic MBC cerebral arteries, the receptor density values in the three age groups were 115 +/- 15, 105 +/- 9, 99 +/- 5 fmol/mg protein, respectively. For fetal and adult Com, high-altitude, long-term hypoxemia was associated with decreases in Ins(1,4,5)P3-R density of 32 (to 58 +/- 5) and 70% (to 109 +/- 12), respectively, from control values (P < 0.01). In MBC cerebral arteries of fetus and adult, hypoxic-associated decreases in Ins(1,4,5)P3-R density from control were 80 (to 23 +/- 3) and 47% (to 53 +/- 7), respectively (P < 0.01). Ins(1,4,5)P3 binding affinity to the receptor averaged 11.8 +/- 0.5 nM and did not vary significantly as a function of vessel type, developmental age, or hypoxia. In Com, but not in MBC, Ins(1,4,5)P3-R density increased dramatically with developmental age. This suggests that differences in Ins(1,4,5)P3-R density values may account, in part, for differences in contractile responses of the two artery types in the several age groups. In response to long-term, high-altitude hypoxia, Ins(1,4,5)P3-R density values in both fetal and adult Com and MBC decreased significantly, as did their NE-induced contraction. This suggests a cellular basis for changes in cerebrovascular contractility in response to long-term hypoxia and that Ins(1,4,5)P3-R may play a role in acclimatization responses to high altitude.

Exhaled nitric oxide decreases upon acute exposure to high-altitude hypoxia

2006 ◽  
Vol 18 (2) ◽  
pp. 196-202 ◽  
Author(s):  
Daniel E. Brown ◽  
Cynthia M. Beall ◽  
Kingman P. Strohl ◽  
Phoebe S. Mills
Keyword(s):  
Nitric Oxide ◽  
High Altitude ◽  
Exhaled Nitric Oxide ◽  
Acute Exposure ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia

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

scholarly journals Integrative plasma proteomic and microRNA analysis of Jersey cattle in response to high-altitude hypoxia

2019 ◽  
Vol 102 (5) ◽  
pp. 4606-4618 ◽  
Author(s):  
Zhiwei Kong ◽  
Chuanshe Zhou ◽  
Bin Li ◽  
Jinzhen Jiao ◽  
Liang Chen ◽  
...  
Keyword(s):  
High Altitude ◽  
Altitude Hypoxia ◽  
Jersey Cattle ◽  
High Altitude Hypoxia
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