Oxygen regulates the effective diffusion distance of nitric oxide in the aortic wall

Abstract

Endothelium-derived nitric oxide (NO) is critical in maintaining vascular tone. Accumulating evidence shows that NO bioavailability is regulated by oxygen concentration. However, it is unclear to what extent the oxygen concentration regulates NO bioavailability in the vascular wall. In this study, a recently developed experimental setup was used to measure the NO diffusion fluxes across the aortic wall at different oxygen concentrations. It was observed that for a constant NO concentration at the endothelial surface, the measured NO diffusion flux out of the adventitial surface at [O2]=0 μM is around 5-fold greater than at [O2]=150 μM, indicating that NO is consumed in the aortic wall in an oxygen-dependent manner. Analysis of experimental data shows that the rate of NO consumption in the aortic wall is first order with respect to [NO] and first order with respect to [O2], and the rate constant k1 was determined as (4.0 ± 0.3)×103 M-1s-1. Computer simulations demonstrate that NO concentration distribution significantly changes with oxygen concentration and the effective NO diffusion distance at low oxygen level ([O2]≤25 μM) is significantly longer than that at high oxygen level ([O2]=200 μM). These results suggest that the oxygen-dependent NO consumption may play an important role in dilating blood vessels during hypoxia by increasing the effective NO diffusion distance.

Nitric Oxide Signaling in the Microcirculation

“…204 This is a much higher NO consumption rate than for direct auto-oxidation, which is first order with O 2 and second order with respect to NO. 205,206 At low O 2 concentrations in the bath, a 5-fold higher NO flux across the wall was found compared with NO flux when the bath O 2 concentration was high.…”

“…205,206 At low O 2 concentrations in the bath, a 5-fold higher NO flux across the wall was found compared with NO flux when the bath O 2 concentration was high. 204 Thus, there is a possibility that some of the increase in NO measured during hypoxia might be attributed to a reduction in NO consumption. Vascular wall NO consumption may be related to the reaction between NO and cytochrome c oxidase.…”

Endothelial NO and O2− production rates differentially regulate oxidative, nitroxidative, and nitrosative stress in the microcirculation

“…We used a constant O 2 concentration of 27 μM to react with NO in the vessels wall. NO consumption in the vessel wall and parenchymal cells may depend on O 2 concentration, which may vary across the wall [79, 80]. The reaction of peroxynitrite with glutathione (GSH) (present at mM levels) was neglected because of a two order magnitude slower reaction rate constant (k=6.6×10 2 M −1 .s −1 ) difference as compared to reaction rate constant with CO 2 (k=1–2×10 4 M −1 .s −1 ) [17, 81].…”

Application of carbon fiber composite minielectrodes for measurement of kinetic constants of nitric oxide decay in solution

“…NO stock solution was prepared as described in previous papers[12, 15]. Briefly, NO was scrubbed of higher nitrogen oxides by passage first through a U-tube containing NaOH pellets and then through a 1 M deaerated (bubbled with 100% argon) KOH solution in a custom-designed apparatus using only glass or stainless steel tubing and fittings.…”

“…Now accumulating evidence shows that NO can also consumed by isolated cells and inside tissues in an oxygen-dependent manner [11, 12]. This inter-regulation between NO and oxygen may play an important physiological role in the body to adapt hypoxic conditions [12–15]. In these research areas, the study of NO metabolism kinetics is very critical and required for a comprehensive understanding of NO physiological functions.…”