Abstract
BackgroundHyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13% O2, frequently occurs in hospitalized patients due to administration of supplemental oxygen. Increasing evidence suggests that hyperoxia induces vasoconstriction in the systemic (micro)circulation, potentially affecting organ perfusion. This study addresses effects of hyperoxia on viability, proliferative capacity, and on pathways affecting vascular tone in cultured human microvascular endothelial cells (hMVEC).MethodshMVEC of the systemic circulation were exposed to graded oxygen fractions of 20, 30, 50, and 95% O2 for 8, 24, and 72 h. These fractions correspond to 152, 228, 380, and 722 mmHg, respectively. Cell proliferation and viability was measured via a proliferation assay, peroxynitrite formation via anti-nitrotyrosine levels, endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) levels via q-PCR and western blot analysis.ResultsExposing hMVEC to 50 and 95% O2 for more than 24 h impaired cell viability and proliferation. Hyperoxia did not significantly affect nitrotyrosine levels, nor eNOS mRNA and protein levels, regardless of the exposure time or oxygen concentration used. Phosphorylation of eNOS at the serine 1177 (S1177) residue and ET-1 mRNA levels were also not significantly affected.ConclusionsExposure of isolated human microvascular endothelial cells to marked hyperoxia for more than 24 h decreases cell viability and proliferation. Our results do not support a role of eNOS mRNA and protein or ET-1 mRNA in the potential vasoconstrictive effects of hyperoxia on isolated hMVEC.
Highlights
Hyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13% O2, frequently occurs in hospitalized patients due to administration of supplemental oxygen
Hyperoxia and cell proliferation A proliferation assay was performed with a pool of three different cell donors to test if microvascular endothelial cells could withstand exposure to hyperoxia (Fig. 1)
Under 20% O2 cells proliferated to 52 × 103 ± 1.8 × 103 cells/cm2 after 3 days, with a typical cobblestone morphology (Fig. 1a, Inset)
Summary
An arterial oxygen pressure of more than 100 mmHg or 13% O2, frequently occurs in hospitalized patients due to administration of supplemental oxygen. Hyperoxia can cause significant hemodynamic alterations [2, 3] and has been reported to induce vasoconstriction in several (cerebral, coronary, skeletal muscle, and retinal) [14,15,16,17], but not all (renal, mesenteric) [18, 19], vascular beds. This vasoconstriction appears mainly to occur at microvascular level, since the diameter of large conduit arteries remains constant [15, 20]. Other studies show that hyperoxia is able to redistribute blood flow which can protect hepatosplanchic organs and the kidneys [22, 23]
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