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Carrasco-Martín C, Alonso-Orgaz S, De la Pinta JC, Marques M, Macaya C, Barrientos A, González MM, García-Mendez A, Mateos-Cáceres PJ, Porres JC, Rico LA, López-Farré AJ

Endothelial hypoxic preconditioning in rat hypoxic isolated aortic segments.

Exp. Physiol.. 2005 Jul;90(4):557-69, PMID: 15769880

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 microg 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.

PHYSIOLOGY