Metabolic Control of Microvascular Networks: Oxygen Sensing and Beyond

The metabolic regulation of blood flow is central to guaranteeing an adequate supply of blood to the tissues and microvascular network stability. It is assumed that vascular reactions to local oxygenation match blood supply to tissue demand via negative-feedback regulation. Low oxygen (O 2 ) levels evoke vasodilatation, and thus an increase of blood flow and oxygen supply, by increasing (decreasing) the release of vasodilatory (vasoconstricting) metabolic signal substances with decreasing partial pressure of O 2 . This review analyses the principles of metabolic vascular control with a focus on the prevailing feedback regulations. We propose the following hypotheses with respect to vessel diameter adaptation. (1) In addition to O 2 -dependent signaling, metabolic vascular regulation can be effected by signal substances produced independently of local oxygenation (reflecting the presence of cells) due to the dilution effect. (2) Control of resting vessel tone, and thus perfusion reserve, could be explained by a vascular activity/hypoxia memory. (3) Vasodilator but not vasoconstrictor signaling can prevent shunt perfusion via signal conduction upstream to feeding arterioles. (4) For low perfusion heterogeneity in the steady state, metabolic signaling from the vessel wall or a perivascular tissue sleeve is optimal. (5) For amplification of perfuReceived: February 26, 2014 Accepted after revision: October 4, 2014 Published online: December 18, 2014 Dr. B. Reglin Department of Physiology, Charité Berlin Charitéplatz 1 DE–10117 Berlin (Germany) E-Mail bettina.reglin @ charite.de © 2014 S. Karger AG, Basel 1018–1172/14/0515–0376$39.50/0