Mechanisms of hyperoxic vasoconstriction

Hyperoxic vasoconstriction does not seem to be of reflexive in origin. Differences in regional distribution, the vascular site of action88 and the decrease in sympathetic activity during hyperoxia11-13,89 argue against this theory.

All authors agree that hyperoxic vasoconstriction is linked to regulatory mechanisms acting at the level of the microcirculation units. Whalen & Nair81,82, were the first to show that cellular PO2 in muscles underwent no change in hyperoxia and that this was due to an adjustment of the microcirculatory blood flow. Duling allocated the action of hyperoxia to the terminal arterioles and the precapillary sphincters72.

Granger74 showed that the higher the level of hyperoxia, the bigger the vessels affected by vasoconstriction. Thus, depending on the degree of hyperoxia, the primary control mechanism involves an effort by the microcirculation to limit gaseous exchanges; if this is unsuccessful, a secondary mechanism comes into play involving vasoconstriction of the proximal (resistance) arteries.

The precise mechanisms of hyperoxic vasoconstriction are still not fully understood. Duling72 showed that oxygen did not have a direct action on vascular smooth muscle cells. The involvement of mediators has been suggested83. The idea of prostaglandins being involved has been abandoned because there is no action of the cyclo-oxygenase inhibitors90,91. Two mechanisms have been suggested :

- Rubanyi & Vanhoute92 showed on the coronary artery rings of cats that the superoxide anion had an inhibitive effect on the EDRF released by the vascular endothelium in response to acetylcholine (which is currently identified as NO) and that hyperoxia encouraged the inactivation. This mechanism can account in part for the vasoconstriction and particularly for the fact that it spreads from the smaller to the larger vessels, but does not fully explain how some terminal arterioles are completely obstructed.

- Jackson84,93 gave evidence of the vasoconstrictive role of leukotrienes in hyperoxic situations and of their inhibition caused by lipo-oxygenase inhibitors and leukotriene receptor antagonists. The cells which produce these have not yet been identified. It seems that it cannot be the arteriolar wall cells since the signal is generated at a distance93. The cells of other vascular walls (venules, capillaries), parenchymal cells or certain blood cells could be producing the leukotrienes. However, the variability in responses depending on the various artery sizes seems to indicate that certain responses must originate from the arteriolar muscle cells.

To summarize, microcirculatory blood flow undergoes a remarkably precise adjustment to oxygenation conditions. Effective protective mechanisms are brought into play to stop pressures of oxygen in the tissues from increasing beyond appropriate levels. There appears to be a hierarchy in these mechanisms, enabling recruitment of defence strategies to vary with the intensity of the hyperoxic challenge. Also they are reversible and discontinue once the hyperoxia ceases. Lastly and most importantly, they do not appear to exceed their objective: i.e., they do not induce paradoxical hypoxia.


HBO administered in the range of pressures used for therapy induces haemodynamic effects both on a central and on a microcirculatory level.

Changes in central haemodynamics mostly involve a decrease in heart rate (effects of pressure and oxygen). Arterial blood pressure tends to increase slightly and cardiac output is maintained or slightly decreased. These are related to adjustment mechanisms that may be harmful in the case of pre-existing cardiac compromise.

On a microcirculatory level, hyperoxic vasoconstriction only occurs in areas where pressures of oxygen increase above normal levels. In previously ischemic areas the increase in oxygen pressure remains close to normal and is not combined with a decrease in local blood flow. On the contrary, the renewed occurrence of vasomotion suggests an improvement in local metabolic conditions.

Thus HBO appears to effect circulation in a way that is beneficial for conditions of hypoperfusion - particularly when these are heterogeneously distributed. Its effects on tissues and especially on cells still need further study.

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