Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training

Michael E. Davis, Hua Cai, Louise McCann, Tohru Fukai, David G. Harrison

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

We have shown that c-Src plays a role in shear stress stimulation of endothelial nitric oxide synthase (eNOS) expression in cultured cells. To examine the role of c-Src in vivo, we exercised C57Blk/6 and c-Src heterozygous (c-Src+/-) mice on a treadmill for 3 wk. Western analysis demonstrated that c-Src+/- mice express less than one-half the normal amount of c-Src. Exercise increased heart rate and blood pressure to identical levels in both strains as determined using radiotelemetry. Exercise training increased eNOS protein >2-fold in the aorta and 1.7-fold in the heart in C57Blk/6 mice but had no effect on eNOS protein levels in c-Src+/- mice. In contrast to exercise, treatment of mice with mevastatin, which stimulates expression of eNOS posttranscriptionally, increased eNOS protein in both strains. Training also increased aortic extracellular superoxide dismutase protein expression, which is regulated by nitric oxide, in C57Blk/6 mice but not in c-Src+/-mice. These data indicate that c-Src has an important role in modulating vascular adaptations to exercise training, in particular increasing eNOS and extracellular superoxide dismutase protein expression.

Original languageEnglish (US)
Pages (from-to)H1449-H1453
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number4 53-4
StatePublished - Apr 1 2003

Fingerprint

Nitric Oxide Synthase Type III
Exercise
Proteins
Superoxide Dismutase
Blood Vessels
Aorta
Cultured Cells
Nitric Oxide
Heart Rate
Blood Pressure

Keywords

  • Extracellular superoxide dismutase
  • Mice
  • Radiotelemetry
  • Western analysis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. / Davis, Michael E.; Cai, Hua; McCann, Louise; Fukai, Tohru; Harrison, David G.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 284, No. 4 53-4, 01.04.2003, p. H1449-H1453.

Research output: Contribution to journalArticle

Davis, Michael E. ; Cai, Hua ; McCann, Louise ; Fukai, Tohru ; Harrison, David G. / Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 284, No. 4 53-4. pp. H1449-H1453.
@article{a5771f01cc0945c198a8780b5c998b07,
title = "Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training",
abstract = "We have shown that c-Src plays a role in shear stress stimulation of endothelial nitric oxide synthase (eNOS) expression in cultured cells. To examine the role of c-Src in vivo, we exercised C57Blk/6 and c-Src heterozygous (c-Src+/-) mice on a treadmill for 3 wk. Western analysis demonstrated that c-Src+/- mice express less than one-half the normal amount of c-Src. Exercise increased heart rate and blood pressure to identical levels in both strains as determined using radiotelemetry. Exercise training increased eNOS protein >2-fold in the aorta and 1.7-fold in the heart in C57Blk/6 mice but had no effect on eNOS protein levels in c-Src+/- mice. In contrast to exercise, treatment of mice with mevastatin, which stimulates expression of eNOS posttranscriptionally, increased eNOS protein in both strains. Training also increased aortic extracellular superoxide dismutase protein expression, which is regulated by nitric oxide, in C57Blk/6 mice but not in c-Src+/-mice. These data indicate that c-Src has an important role in modulating vascular adaptations to exercise training, in particular increasing eNOS and extracellular superoxide dismutase protein expression.",
keywords = "Extracellular superoxide dismutase, Mice, Radiotelemetry, Western analysis",
author = "Davis, {Michael E.} and Hua Cai and Louise McCann and Tohru Fukai and Harrison, {David G.}",
year = "2003",
month = "4",
day = "1",
language = "English (US)",
volume = "284",
pages = "H1449--H1453",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 53-4",

}

TY - JOUR

T1 - Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training

AU - Davis, Michael E.

AU - Cai, Hua

AU - McCann, Louise

AU - Fukai, Tohru

AU - Harrison, David G.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - We have shown that c-Src plays a role in shear stress stimulation of endothelial nitric oxide synthase (eNOS) expression in cultured cells. To examine the role of c-Src in vivo, we exercised C57Blk/6 and c-Src heterozygous (c-Src+/-) mice on a treadmill for 3 wk. Western analysis demonstrated that c-Src+/- mice express less than one-half the normal amount of c-Src. Exercise increased heart rate and blood pressure to identical levels in both strains as determined using radiotelemetry. Exercise training increased eNOS protein >2-fold in the aorta and 1.7-fold in the heart in C57Blk/6 mice but had no effect on eNOS protein levels in c-Src+/- mice. In contrast to exercise, treatment of mice with mevastatin, which stimulates expression of eNOS posttranscriptionally, increased eNOS protein in both strains. Training also increased aortic extracellular superoxide dismutase protein expression, which is regulated by nitric oxide, in C57Blk/6 mice but not in c-Src+/-mice. These data indicate that c-Src has an important role in modulating vascular adaptations to exercise training, in particular increasing eNOS and extracellular superoxide dismutase protein expression.

AB - We have shown that c-Src plays a role in shear stress stimulation of endothelial nitric oxide synthase (eNOS) expression in cultured cells. To examine the role of c-Src in vivo, we exercised C57Blk/6 and c-Src heterozygous (c-Src+/-) mice on a treadmill for 3 wk. Western analysis demonstrated that c-Src+/- mice express less than one-half the normal amount of c-Src. Exercise increased heart rate and blood pressure to identical levels in both strains as determined using radiotelemetry. Exercise training increased eNOS protein >2-fold in the aorta and 1.7-fold in the heart in C57Blk/6 mice but had no effect on eNOS protein levels in c-Src+/- mice. In contrast to exercise, treatment of mice with mevastatin, which stimulates expression of eNOS posttranscriptionally, increased eNOS protein in both strains. Training also increased aortic extracellular superoxide dismutase protein expression, which is regulated by nitric oxide, in C57Blk/6 mice but not in c-Src+/-mice. These data indicate that c-Src has an important role in modulating vascular adaptations to exercise training, in particular increasing eNOS and extracellular superoxide dismutase protein expression.

KW - Extracellular superoxide dismutase

KW - Mice

KW - Radiotelemetry

KW - Western analysis

UR - http://www.scopus.com/inward/record.url?scp=0037377576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037377576&partnerID=8YFLogxK

M3 - Article

C2 - 12595302

AN - SCOPUS:0037377576

VL - 284

SP - H1449-H1453

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4 53-4

ER -