Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase

Thomas Cascino, Gabor Csanyi, Imad Al Ghouleh, Augusto C. Montezano, Rhian M. Touyz, Mounir J. Haurani, Patrick J. Pagano

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The role of adventitia-derived reactive oxygen species (ROS) in vascular disease and impaired vascular relaxation is not clear. Based on robust adventitial ROS generation and effects on MAPK involvement in vascular dysfunction, we hypothesized that adventitia-derived ROS hydrogen peroxide (H 2O 2) impairs vascular relaxation through activation of medial smooth muscle p38 MAPK. By using a novel in vivo model, the adventitial surface of rat carotid arteries was bathed in situ for 90  min with vehicle, angiotensin II (AngII; 500 nM), AngII+H 2O 2-scavenger catalase (3,000  U/ml), AngII+p38 MAPK inhibitor SB203580 (10  μM), or AngII+superoxide dismutase (SOD; 150  U/ml). After these in vivo treatments, ex vivo tone measurements on isolated vessels revealed that periadventitial application of AngII impaired both acetylcholine-induced (endothelium-dependent) and sodium nitroprusside-induced (endothelium-independent) relaxations. In vivo coincubation with catalase or SB203580 significantly improved, but SOD exacerbated AngII-induced impairment of in vitro endothelium-dependent and-independent vascular relaxations. Western blots of vascular media, separated from the adventitia, demonstrated increased medial p38 MAPK activation and decreased medial phosphatase SHP-2 activity in AngII-treated vessels. These effects were reversed by in vivo periadventitial addition of catalase. These findings provide the first evidence that adventitia-derived H 2O 2 participates in vascular dysfunction through p38 MAPK activation and SHP-2 inhibition.

Original languageEnglish (US)
Pages (from-to)1507-1515
Number of pages9
JournalAntioxidants and Redox Signaling
Volume15
Issue number6
DOIs
StatePublished - Sep 15 2011
Externally publishedYes

Fingerprint

Adventitia
p38 Mitogen-Activated Protein Kinases
Carotid Arteries
Hydrogen Peroxide
Smooth Muscle Myocytes
Muscle
Rats
Cells
Catalase
Reactive Oxygen Species
Blood Vessels
Chemical activation
Endothelium
Nitroprusside
Phosphoric Monoester Hydrolases
Angiotensin II
Acetylcholine
Superoxide Dismutase
Tunica Media
Cohort Effect

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase. / Cascino, Thomas; Csanyi, Gabor; Al Ghouleh, Imad; Montezano, Augusto C.; Touyz, Rhian M.; Haurani, Mounir J.; Pagano, Patrick J.

In: Antioxidants and Redox Signaling, Vol. 15, No. 6, 15.09.2011, p. 1507-1515.

Research output: Contribution to journalArticle

Cascino, Thomas ; Csanyi, Gabor ; Al Ghouleh, Imad ; Montezano, Augusto C. ; Touyz, Rhian M. ; Haurani, Mounir J. ; Pagano, Patrick J. / Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase. In: Antioxidants and Redox Signaling. 2011 ; Vol. 15, No. 6. pp. 1507-1515.
@article{4dcc844b93e24fdaa197634fa9fc1087,
title = "Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase",
abstract = "The role of adventitia-derived reactive oxygen species (ROS) in vascular disease and impaired vascular relaxation is not clear. Based on robust adventitial ROS generation and effects on MAPK involvement in vascular dysfunction, we hypothesized that adventitia-derived ROS hydrogen peroxide (H 2O 2) impairs vascular relaxation through activation of medial smooth muscle p38 MAPK. By using a novel in vivo model, the adventitial surface of rat carotid arteries was bathed in situ for 90{\^a}€‰ min with vehicle, angiotensin II (AngII; 500 nM), AngII+H 2O 2-scavenger catalase (3,000{\^a}€‰ U/ml), AngII+p38 MAPK inhibitor SB203580 (10{\^a}€‰ μM), or AngII+superoxide dismutase (SOD; 150{\^a}€‰ U/ml). After these in vivo treatments, ex vivo tone measurements on isolated vessels revealed that periadventitial application of AngII impaired both acetylcholine-induced (endothelium-dependent) and sodium nitroprusside-induced (endothelium-independent) relaxations. In vivo coincubation with catalase or SB203580 significantly improved, but SOD exacerbated AngII-induced impairment of in vitro endothelium-dependent and-independent vascular relaxations. Western blots of vascular media, separated from the adventitia, demonstrated increased medial p38 MAPK activation and decreased medial phosphatase SHP-2 activity in AngII-treated vessels. These effects were reversed by in vivo periadventitial addition of catalase. These findings provide the first evidence that adventitia-derived H 2O 2 participates in vascular dysfunction through p38 MAPK activation and SHP-2 inhibition.",
author = "Thomas Cascino and Gabor Csanyi and {Al Ghouleh}, Imad and Montezano, {Augusto C.} and Touyz, {Rhian M.} and Haurani, {Mounir J.} and Pagano, {Patrick J.}",
year = "2011",
month = "9",
day = "15",
doi = "10.1089/ars.2010.3631",
language = "English (US)",
volume = "15",
pages = "1507--1515",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

TY - JOUR

T1 - Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase

AU - Cascino, Thomas

AU - Csanyi, Gabor

AU - Al Ghouleh, Imad

AU - Montezano, Augusto C.

AU - Touyz, Rhian M.

AU - Haurani, Mounir J.

AU - Pagano, Patrick J.

PY - 2011/9/15

Y1 - 2011/9/15

N2 - The role of adventitia-derived reactive oxygen species (ROS) in vascular disease and impaired vascular relaxation is not clear. Based on robust adventitial ROS generation and effects on MAPK involvement in vascular dysfunction, we hypothesized that adventitia-derived ROS hydrogen peroxide (H 2O 2) impairs vascular relaxation through activation of medial smooth muscle p38 MAPK. By using a novel in vivo model, the adventitial surface of rat carotid arteries was bathed in situ for 90  min with vehicle, angiotensin II (AngII; 500 nM), AngII+H 2O 2-scavenger catalase (3,000  U/ml), AngII+p38 MAPK inhibitor SB203580 (10  μM), or AngII+superoxide dismutase (SOD; 150  U/ml). After these in vivo treatments, ex vivo tone measurements on isolated vessels revealed that periadventitial application of AngII impaired both acetylcholine-induced (endothelium-dependent) and sodium nitroprusside-induced (endothelium-independent) relaxations. In vivo coincubation with catalase or SB203580 significantly improved, but SOD exacerbated AngII-induced impairment of in vitro endothelium-dependent and-independent vascular relaxations. Western blots of vascular media, separated from the adventitia, demonstrated increased medial p38 MAPK activation and decreased medial phosphatase SHP-2 activity in AngII-treated vessels. These effects were reversed by in vivo periadventitial addition of catalase. These findings provide the first evidence that adventitia-derived H 2O 2 participates in vascular dysfunction through p38 MAPK activation and SHP-2 inhibition.

AB - The role of adventitia-derived reactive oxygen species (ROS) in vascular disease and impaired vascular relaxation is not clear. Based on robust adventitial ROS generation and effects on MAPK involvement in vascular dysfunction, we hypothesized that adventitia-derived ROS hydrogen peroxide (H 2O 2) impairs vascular relaxation through activation of medial smooth muscle p38 MAPK. By using a novel in vivo model, the adventitial surface of rat carotid arteries was bathed in situ for 90  min with vehicle, angiotensin II (AngII; 500 nM), AngII+H 2O 2-scavenger catalase (3,000  U/ml), AngII+p38 MAPK inhibitor SB203580 (10  μM), or AngII+superoxide dismutase (SOD; 150  U/ml). After these in vivo treatments, ex vivo tone measurements on isolated vessels revealed that periadventitial application of AngII impaired both acetylcholine-induced (endothelium-dependent) and sodium nitroprusside-induced (endothelium-independent) relaxations. In vivo coincubation with catalase or SB203580 significantly improved, but SOD exacerbated AngII-induced impairment of in vitro endothelium-dependent and-independent vascular relaxations. Western blots of vascular media, separated from the adventitia, demonstrated increased medial p38 MAPK activation and decreased medial phosphatase SHP-2 activity in AngII-treated vessels. These effects were reversed by in vivo periadventitial addition of catalase. These findings provide the first evidence that adventitia-derived H 2O 2 participates in vascular dysfunction through p38 MAPK activation and SHP-2 inhibition.

UR - http://www.scopus.com/inward/record.url?scp=79961197713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961197713&partnerID=8YFLogxK

U2 - 10.1089/ars.2010.3631

DO - 10.1089/ars.2010.3631

M3 - Article

VL - 15

SP - 1507

EP - 1515

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 6

ER -