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Adventitial Hydrogen Peroxide (H2O2) Impairs Rat Carotid Artery Relaxation via Medial p38 MAPK
Author(s) -
Cascino Thomas M.,
Haurani Mounir J.,
Pagano Patrick J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.758.22
Subject(s) - adventitia , chemistry , vascular smooth muscle , endocrinology , mapk/erk pathway , medicine , angiotensin ii , p38 mitogen activated protein kinases , catalase , endothelium , kinase , biology , oxidative stress , biochemistry , receptor , smooth muscle
The vascular adventitia is a major source of H2O2. H2O2 activates smooth muscle p38 mitogen activated protein kinase (p38 MAPK). We postulated that adventitia‐derived H2O2 impairs relaxation via medial kinase activation. Isolated rat carotid arteries were bathed perivascularly (in situ) over 90 min in vehicle, angiotensin II (AngII, 500 nM), AngII + H2O2‐scavenger catalase or AngII + p38 MAPK inhibitor, then placed in myographs and preconstricted. Both acetylcholine (ACh)‐induced endothelium‐dependent and sodium nitroprusside (SNP)‐induced endothelium‐independent relaxations were impaired by AngII (p < 0.05). Catalase partially reversed the AngII effect on ACh‐induced relaxation and reversed impairment of SNP‐induced relaxations (p < 0.05). The p38 MAPK inhibitor SB203580 partially ameliorated the impairment of SNP‐induced relaxations and reversed the AngII effect on ACh‐induced relaxation (p < 0.05). In separate pretreated vessels, the media was dissected, homogenized and Western blots run for phosphorylated vs. total p38 MAPK. AngII activated medial p38 MAPK, but catalase inhibited this. These data suggest AngII elicits release of adventitial H2O2, impairing both endothelium‐dependent and –independent relaxation via the p38 MAPK pathway in the media. The data provide evidence of a significant paracrine signaling role of vascular adventitial H2O2 on vascular function.