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.

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

High altitude-induced changes in alpha1-adrenergic receptors and Ins(1,4,5)P3 responses in cerebral arteries

1997 ◽  
Vol 272 (2) ◽  
pp. R669-R674 ◽  
Author(s):  
N. Ueno ◽  
Y. Zhao ◽  
L. Zhang ◽  
L. D. Longo
Keyword(s):  
High Altitude ◽  
Adrenergic Receptor ◽  
Cerebral Arteries ◽  
Control Value ◽  
Density Values ◽  
High Altitude Acclimatization ◽  
Normoxic Control ◽  
Near Term ◽  
Induced Changes

In response to high-altitude long-term hypoxemia, the cerebral arteries of fetal and adult sheep show decreased contractile responses to norepinephrine (NE) and other agonists. To test the hypothesis that hypoxia-induced developmental and vessel specific cerebral artery contractility changes are mediated, in part, by changes in alpha1-adrenergic receptor (alpha1-AR) density and/or NE-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] responses, we performed the following study. In common carotid (Com) and main branch cerebral (MBC) arteries from normoxic adult ewes and near-term fetuses and those acclimatized to high altitude (3,820 m), we quantified alpha1-AR density (maximal binding in fmol/mg protein) and affinity (dissociation constant in nM) with the alpha1-AR antagonist [3H]prazosin. In addition, we quantified NE-induced Ins(1,4,5)P3 responses in these arteries. With long-term hypoxemia, alpha1-AR density in fetal and adult Com decreased 75% (from 113 +/- 18 to 28 +/- 5 fmol/mg protein) and 66% (from 54 +/- 3 to 18 +/- 4 fmol/mg protein), respectively, from normoxic control values. alpha1-AR density of the fetal and adult MBC decreased 76% (from 47 +/- 4 to 11 +/- 1 fmol/mg protein) and 61% (from 23 +/- 3 to 9 +/- 3 fmol/mg protein), respectively, from controls. In hypoxemic adult Com, the NE-induced Ins(1,4,5)P3 response decreased 51% (from 309 +/- 38 to 151 +/- 24%) from the control value. In fetal and adult MBC, long-term hypoxemia was associated with decreases of 35% (from 345 +/- 40 to 225 +/- 30%) and 44% (from 355 +/- 55 to 199 +/- 16%), respectively, from control values. We conclude that in the adult Com and MBC vessels, acclimatization to high-altitude, long-term hypoxemia was associated with significant decreases in both alpha1-AR density values and Ins(1,4,5)P3 responses to NE. Similarly, in the fetal MBC arteries, high-altitude hypoxemia was associated with marked attenuation of both alpha1-AR density and NE-induced Ins(1,4,5)P3 responses. The magnitude of decreases in NE-induced Ins(1,4,5)P3 responses in these vessels correlated fairly well with the decreases in alpha1-AR density. These findings suggest that changes in noradrenergic receptor-second messenger coupling may play a role in altered cerebrovascular tone in association with high-altitude acclimatization and other forms of long-term hypoxia in both fetus and adult.

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.

Pre- and postjunctional α2-adrenergic receptors in fetal and adult ovine cerebral arteries

2002 ◽  
Vol 282 (6) ◽  
pp. R1654-R1662 ◽  
Author(s):  
John M. Bishai ◽  
Luit Penninga ◽  
Roel Nijland ◽  
Rogier Meulenaar ◽  
Ciprian P. Gheorghe ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Dose Response ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cerebral Arteries ◽  
Age Groups ◽  
Significant Component ◽  
Contractile Responses ◽  
Developmental Age

In ovine cerebral arteries, adrenergic-mediated vasoconstrictor responses differ significantly with developmental age. We tested the hypothesis that, in part, these differences are a consequence of altered α2-adrenergic receptor (α2-AR) density and/or affinity. In fetal (∼140 days) and adult sheep, we measured α2-AR density and affinity with the antagonist [3H]idazoxan in main branch cerebral arteries and other vessels. We also quantified contractile responses in middle cerebral artery (MCA) to norepinephrine (NE) or phenylephrine in the presence of the α2-AR antagonists yohimbine and idazoxan and contractile responses to the α2-AR agonists clonidine and UK-14304. In fetal and adult cerebral artery homogenates, α2-AR density was 201 ± 18 and 52 ± 6 fmol/mg protein, respectively ( P< 0.01); however, antagonist affinity values did not differ. In fetal, but not adult, MCA, 10−7 M yohimbine significantly decreased the pD2 for NE-induced tension in the presence of 3 × 10−5 M cocaine, 10−5 M deoxycorticosterone, and 10−6 M tetrodotoxin. In fetal, but not adult, MCA, UK-14304 induced a significant decrease in pD2 for the phenylephrine dose-response relation. In addition, stimulation-evoked fractional NE release was significantly greater in fetal than in adult cerebral arteries. In the presence of 10−6 M idazoxan to block α2-AR-mediated inhibition of prejunctional NE release, the fractional NE release was significantly increased in both age groups. We conclude that in fetal and adult ovine cerebral arteries, α2-AR appear to be chiefly prejunctional. Nonetheless, the fetal cerebral arteries appear to have a significant component of postjunctional α2-AR.

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
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