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Origins of variation in conducted vasomotor responses

  • INTEGRATIVE PHYSIOLOGY
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Abstract

Regulation of blood flow in the microcirculation depends on synchronized vasomotor responses. The vascular conducted response is a synchronous dilatation or constriction, elicited by a local electrical event that spreads along the vessel wall. Despite the underlying electrical nature, however, the efficacy of conducted responses varies significantly between different initiating stimuli within the same vascular bed as well as between different vascular beds following the same stimulus. The differences have stimulated proposals of different mechanisms to account for the experimentally observed variation. Using a computational approach that allows for introduction of structural and electrophysiological heterogeneity, we systematically tested variations in both arteriolar electrophysiology and modes of stimuli. Within the same vessel, our simulations show that conduction efficacy is influenced by the type of cell being stimulated and, in case of depolarization, by the stimulation strength. Particularly, simultaneous stimulation of both endothelial and vascular smooth muscle cells augments conduction. Between vessels, the specific electrophysiology determines membrane resistance and conduction efficiency—notably depolarization or radial currents reduce electrical spread. Random cell-cell variation, ubiquitous in biological systems, only cause small or no reduction in conduction efficiency. Collectively, our simulations can explain why CVRs from hyperpolarizing stimuli tend to conduct longer than CVRs from depolarizing stimuli and why agonists like acetylcholine induce CVRs that tend to conduct longer than electrical injections. The findings demonstrate that although substantial heterogeneity is observed in conducted responses, it can be largely ascribed to the origin of electrical stimulus combined with the specific electrophysiological properties of the arteriole. We conclude by outlining a set of “principles of electrical conduction” in the microcirculation.

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Acknowledgments

The work is part of the Dynamical Systems Interdisciplinary Network, University of Copenhagen. BOH is supported by Arvid Nilssons Fond and the Danish Council for Independent Research (DFF – 1333-00172). DGW is supported by an operating grant from the Canadian Institute of Health Research. The authors would like to thank Preben Graae Sørensen for the use of his computing cluster.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark

    Bjørn Olav Hald, Niels-Henrik Holstein-Rathlou & Jens Christian Brings Jacobsen

  2. Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada

    Donald G. Welsh

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  1. Bjørn Olav Hald
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  2. Donald G. Welsh
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  3. Niels-Henrik Holstein-Rathlou
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  4. Jens Christian Brings Jacobsen
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Correspondence to Bjørn Olav Hald.

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Hald, B.O., Welsh, D.G., Holstein-Rathlou, NH. et al. Origins of variation in conducted vasomotor responses. Pflugers Arch - Eur J Physiol 467, 2055–2067 (2015). https://doi.org/10.1007/s00424-014-1649-1

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  • DOI: https://doi.org/10.1007/s00424-014-1649-1

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