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This Article Full Text Full Text (PDF) All Versions of this Article: 90/4/557    most recent expphysiol.2005.030163v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Carrasco-Martín, C. Articles by López-Farré, A. J Search for Related Content PubMed PubMed Citation Articles by Carrasco-Martín, C. Articles by López-Farré, A. J Related Collections Vascular

¹ Digestive Research Laboratory, Fundación Jiménez Díaz² Cardiovascular Research Unit³ Nephrology Department, Hospital Clínico San Carlos, Madrid 28040, Spain

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 serine¹¹⁷⁷ phosphorylated endothelial nitric oxide synthase (eNOS) (ser¹¹⁷⁷-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: IC₅₀, 5 ± 2.5 x 10^–8 mol l^–1; HR: IC₅₀, 3 ± 1.2 x 10^–7 mol l^–1; P < 0.05). Ach-dependent vasodilatation was improved by P + HR. The content of ser¹¹⁷⁷-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 ser¹¹⁷⁷-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 ser¹¹⁷⁷-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.

(Received 28 January 2005; accepted after revision 4 March 2005; first published online 15 March 2005)
Corresponding author A. J. López-Farré: Cardiovascular Research Unit, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, Madrid 28040, Spain. Email: ajlopez.hcsc{at}salud.madrid.org