OBJECTIVE: The inability of the organism to appropriately respond to hypoxia results in abnormal cell metabolism and function. Hypoxia-induced angiogenesis seems to be suppressed in experimental models of hypertension; however, this hypothesis has not been tested in humans. We examined changes in endothelial biomarkers and vascular chemoattraction/angiogenic capacity in response to isocapnic hypoxia in hypertensive men. METHODS: Twelve normotensive (38 ± 10 years) and nine hypertensive men (45 ± 11 years) were exposed to 5-min trials of normoxia (21% O2) and isocapnic hypoxia (10% O2). During the last minute of each trial, venous blood was drawn. Endothelial progenitor cells (EPCs; CD45/CD34/VEGFR2), endothelial microvesicles (apoptotic EMVs, CD42b/CD31/AnnexinV; endothelial activation, CD62E/CD144), nitrite, vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) were measured. RESULTS: During normoxia, EPCs, nitrite, endothelial activation, and SDF-1 were similar between groups, whereas VEGF was lower (P = 0.02) and apoptotic EMVs tended to increase (P = 0.07) in hypertensive men. During isocapnic hypoxia, endothelial activation increased in both groups (normotensive, P = 0.007 vs. normoxia; hypertensive, P = 0.006 vs. normoxia), whereas EMVs were higher only in the hypertensive group (P = 0.03 vs. normotensive). EPCs (P = 0.01 vs. normoxia; P = 0.03 vs. hypertensive men), NO (P = 0.01 vs. normoxia; P = 0.04 vs. hypertensive), and VEGF (P = 0.02 vs. normoxia; P = 0.0005 vs. hypertensive) increased only in normotensive individuals in response to isocapnic hypoxia. SDF-1 did not change in either group. CONCLUSION: These results suggest that hypertension-induced impairment in angiogenesis in response to isocapnic hypoxia is related to disrupted NO bioavailability, VEGF chemotactic signaling, and EPC mobilization.
OBJECTIVE: The inability of the organism to appropriately respond to hypoxia results in abnormal cell metabolism and function. Hypoxia-induced angiogenesis seems to be suppressed in experimental models of hypertension; however, this hypothesis has not been tested in humans. We examined changes in endothelial biomarkers and vascular chemoattraction/angiogenic capacity in response to isocapnic hypoxia in hypertensivemen. METHODS: Twelve normotensive (38 ± 10 years) and nine hypertensivemen (45 ± 11 years) were exposed to 5-min trials of normoxia (21% O2) and isocapnic hypoxia (10% O2). During the last minute of each trial, venous blood was drawn. Endothelial progenitor cells (EPCs; CD45/CD34/VEGFR2), endothelial microvesicles (apoptotic EMVs, CD42b/CD31/AnnexinV; endothelial activation, CD62E/CD144), nitrite, vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) were measured. RESULTS: During normoxia, EPCs, nitrite, endothelial activation, and SDF-1 were similar between groups, whereas VEGF was lower (P = 0.02) and apoptotic EMVs tended to increase (P = 0.07) in hypertensivemen. During isocapnic hypoxia, endothelial activation increased in both groups (normotensive, P = 0.007 vs. normoxia; hypertensive, P = 0.006 vs. normoxia), whereas EMVs were higher only in the hypertensive group (P = 0.03 vs. normotensive). EPCs (P = 0.01 vs. normoxia; P = 0.03 vs. hypertensivemen), NO (P = 0.01 vs. normoxia; P = 0.04 vs. hypertensive), and VEGF (P = 0.02 vs. normoxia; P = 0.0005 vs. hypertensive) increased only in normotensive individuals in response to isocapnic hypoxia. SDF-1 did not change in either group. CONCLUSION: These results suggest that hypertension-induced impairment in angiogenesis in response to isocapnic hypoxia is related to disrupted NO bioavailability, VEGF chemotactic signaling, and EPC mobilization.