Implications Of Acute Exercise And Inspiratory Hypoxia For Systemic NO Bioavailability

Abstract

Systemic vascular nitric oxide (NO) bioavailability is known to play a key role in regulation of vascular tone at rest in Normoxic (N) and Hypoxic (H) conditions (Maher et al. Circulation 2008. 117 (5) 594-7). However, the effect of altered oxygen delivery as a function of exercise and inspiratory hypoxia and subsequent implications for NO metabolites remains unknown. PURPOSE: The present study examined the effects of physical exercise and H on NO metabolites in the systemic circulation. Specifically, we hypothesized that exercise would result in a net loss of NO metabolites which would be compounded in hypoxia due to a) PO2 mediated re-apportionment and/or b) oxidative inactivation. METHODS: Fourteen healthy males aged 24 (mean) ± 5 (SD) years performed two incremental tests to volitional exhaustion in N (21%O2) and H (∼12%O2). Maximal oxygen consumption (VO2max) was measured off line using the Douglas bag method and arterial haemoglobin oxygen saturation (SaO2) via pulse oximetry. Blood samples were taken from an antecubital vein before and immediately after exercise for determination of PO2 and plasma concentrations of nitrite (NO), nitrate (NO) and S-nitrosothiols (RSNO) via ozone-based chemiluminescence using modified tri-iodide/vanadium reagents. Data were analyzed with a two-way repeated measures ANOVA and post-hoc Bonferroni-corrected paired samples t-tests and relationships between variables by a Pearson Product Moment correlation coefficient. RESULTS: H decreased SaO2 (N: 96 ± 1 vs H: 77± 4%, P < 0.05) and subsequently VO2max (N: 3.92 ± 0.30 vs H: 3.00 ± 0.17 L/min, P < 0.05). Total NO did not change as a result of exercise and hypoxia (N: -0.4 ± 6.3 vs H: -1.2 ± 7.7μmol). The exercise-induced reduction in NO (N; -137 ± 93 norm vs. H: -78 ± 99 nmol) was mirrored by an exercise-induced increase in RSNO (N: + 11 ± 31 vs. H: + 21 ± 16 nmol (P < 0.05). A more marked reduction in NO was observed during N exercise (P = 0.07). CONCLUSION: These findings demonstrate an exercise induced re-apportionment of NO across the metabolite pool (from nitrite to RSNO) that may help conserve vascular O2 delivery which is especially important in H. Alternatively the reduction in nitrite and tendency towards a decrease total NO may reflect oxidative inactivation.