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Endothelial hypoxic preconditioning in rat hypoxic isolated aortic segments
Author(s) -
CarrascoMartín Carolina,
AlonsoOrgaz Sergio,
De la Pinta Juan C.,
Marques Maria,
Macaya Carlos,
Barrientos Alberto,
González Maria M.,
GarcíaMéndez Antonio,
MateosCáceres Petra Jiménez,
Porres Juan C.,
Rico Luis A.,
LópezFarré Antonio J.
Publication year - 2005
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.030163
Subject(s) - enos , vasodilation , hypoxia (environmental) , medicine , chemistry , endocrinology , endothelial dysfunction , endothelium , nitric oxide , endothelial nos , nitric oxide synthase , oxygen , organic chemistry
Our aim was to analyse endothelial hypoxic preconditioning after hypoxia–reperfusion (HR). Endothelial functionality was analysed through the vasorelaxation responses to acetylcholine (Ach) and the level of serine 1177 phosphorylated endothelial nitric oxide synthase (eNOS) (ser 1177 ‐eNOS) measured by Western blot in in vitro hypoxic preconditioned (P + HR) isolated rat aortic segments. Relaxation in response to Ach was reduced in phenylephrine‐precontracted aortic segments after HR (control: IC 50 , 5 ± 2.5 × 10 −8 mol l −1 ; HR: IC 50 , 3 ± 1.2 × 10 −7 mol l −1 ; P < 0.05). Ach‐dependent vasodilatation was improved by P + HR. The content of ser 1177 ‐eNOS in the HR segments was 1.5‐fold lower than in P + HR. Confocal microscopy showed an increased content of both superoxide anion and peroxynitrite in the vascular wall of HR aortic segments, which it was reduced by P + HR. Geldanamycin (10 μg ml −1 ), an agent known to inhibit heat shock protein 90 (hsp90), reduced the level of ser 1177 ‐eNOS in P + HR aortic segments. However in the presence of geldanamycin, endothelial hypoxic preconditioning persisted. We conclude that short periods of hypoxia induced endothelial hypoxic preconditioning that was accompanied by enhanced levels of ser 1177 ‐eNOS in the vascular wall. The fact that endothelial hypoxic preconditioning persisted in the presence of geldanamycin suggests that other molecular mechanisms are involved in the endothelial adaptation to HR injury.