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

Emmanuel M Ngu, Lubo Zhang, William J. Pearce, Sue P. Duckles, John Buchholz

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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, Nω-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.

Original languageEnglish (US)
Pages (from-to)724-732
Number of pages9
JournalJournal of Applied Physiology
Volume94
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

Fingerprint

Cerebral Arteries
Middle Cerebral Artery
Sheep
Nitric Oxide Synthase Type I
Altitude Sickness
Nitric Oxide
NG-Nitroarginine Methyl Ester
Adrenergic Agents
Electric Stimulation
Norepinephrine
Hypoxia
Penicillamine
Nitric Oxide Donors
Tetrodotoxin
Neurotoxins
Luminescence
Nitric Oxide Synthase
Western Blotting
High Pressure Liquid Chromatography

Keywords

  • Cerebrovascular circulation
  • Development and sympathetic nerve function
  • High-altitude hypoxemia
  • Neuronal nitric oxide synthase nerves
  • Norepinephrine release
  • Recombinant neuronal nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Chronic hypoxia alters the function of NOS nerves in cerebral arteries of near-term fetal and adult sheep. / Ngu, Emmanuel M; Zhang, Lubo; Pearce, William J.; Duckles, Sue P.; Buchholz, John.

In: Journal of Applied Physiology, Vol. 94, No. 2, 01.02.2003, p. 724-732.

Research output: Contribution to journalArticle

Ngu, Emmanuel M ; Zhang, Lubo ; Pearce, William J. ; Duckles, Sue P. ; Buchholz, John. / Chronic hypoxia alters the function of NOS nerves in cerebral arteries of near-term fetal and adult sheep. In: Journal of Applied Physiology. 2003 ; Vol. 94, No. 2. pp. 724-732.
@article{40a809627f8a4083894420af3f836dee,
title = "Chronic hypoxia alters the function of NOS nerves in cerebral arteries of near-term fetal and adult sheep",
abstract = "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, Nω-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.",
keywords = "Cerebrovascular circulation, Development and sympathetic nerve function, High-altitude hypoxemia, Neuronal nitric oxide synthase nerves, Norepinephrine release, Recombinant neuronal nitric oxide synthase",
author = "Ngu, {Emmanuel M} and Lubo Zhang and Pearce, {William J.} and Duckles, {Sue P.} and John Buchholz",
year = "2003",
month = "2",
day = "1",
doi = "10.1152/japplphysiol.00771.2002",
language = "English (US)",
volume = "94",
pages = "724--732",
journal = "Journal of Applied Physiology Respiratory Environmental and Exercise Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Chronic hypoxia alters the function of NOS nerves in cerebral arteries of near-term fetal and adult sheep

AU - Ngu, Emmanuel M

AU - Zhang, Lubo

AU - Pearce, William J.

AU - Duckles, Sue P.

AU - Buchholz, John

PY - 2003/2/1

Y1 - 2003/2/1

N2 - 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, Nω-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.

AB - 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, Nω-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.

KW - Cerebrovascular circulation

KW - Development and sympathetic nerve function

KW - High-altitude hypoxemia

KW - Neuronal nitric oxide synthase nerves

KW - Norepinephrine release

KW - Recombinant neuronal nitric oxide synthase

UR - http://www.scopus.com/inward/record.url?scp=0037308832&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037308832&partnerID=8YFLogxK

U2 - 10.1152/japplphysiol.00771.2002

DO - 10.1152/japplphysiol.00771.2002

M3 - Article

VL - 94

SP - 724

EP - 732

JO - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology

JF - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology

SN - 8750-7587

IS - 2

ER -