Main content

THE ROLE OF CAPILLARIES AS SIGNAL INTEGRATORS IN THE SKELETAL MUSCLE MICROVASCULATURE

Show full item record

Title: THE ROLE OF CAPILLARIES AS SIGNAL INTEGRATORS IN THE SKELETAL MUSCLE MICROVASCULATURE
Author: Lamb, Iain R.
Department: Department of Human Health and Nutritional Sciences
Program: Human Health and Nutritional Sciences
Advisor: Murrant, Coral L.
Abstract: Arterioles are thought to be important in coordinating skeletal muscle blood flow, but they lack a consistent architectural relationship with skeletal muscle and the signalling capability to direct flow to specific fibres. However, capillaries have a conserved architectural proximity with skeletal muscle fibers and can direct flow by signalling the upstream arteriole controlling their perfusion. Signalling mechanisms at the capillary level remain understudied. Therefore, we aimed to characterize capillary signalling by investigating i) whether redundancies occur between vasodilators at the capillary level and ii) if a second pathway is involved in mediating the capillary conducted response. Using the hamster cremaster muscle, we stimulated capillaries with vasodilators in the absence and presence of a second vasodilator. Using K+, ADO and SNAP (NO-donor) we demonstrated that vasodilators can inhibit one another's vasodilatory effects. We found that KCl significantly attenuated SNAP- and ADO-induced vasodilatations, ADO attenuated KCl and SNAP-induced vasodilatations and NO attenuated KCl-induced vasodilatation. During muscle contraction, only when K+ was inhibited were NO or ADO able to elicit a detectable vasodilatation. Therefore, we have demonstrated inhibitory interactions occur between vasodilators at capillary. As these interactions occur during muscle contraction indicate that redundancies between vasodilators are physiologically relevant and influence vasodilatation during active hyperaemia. We sought to determine the role pannexin/purinergic-dependent signalling plays in mediating the capillary conducted response. Using hamster cremaster muscle, we stimulated capillaries via vasodilators (KCl, ADO, PIN, SNAP and ACh) in the absence and presence of blockers of the pannexin/purinergic-dependent pathways (MEF, PROB and SUR) and gap-junction dependent pathway (HALO). We found that KCl-, ADO- and PIN-induced conducted responses were pannexin/purinergic-dependent, NO-induced upstream vasodilatation was GJ-dependent while ACh upstream vasodilatations were both GJ- and pannexin/purinergic-dependent. To establish the physiological relevance of pannexin/purinergic-dependent signalling we stimulated capillaries via muscle contraction in the absence and presence of the MEF, SUR, and HALO. We demonstrated that during contraction the conducted response could be propagated via either pathway, however this was dependent on contraction parameters. These data demonstrate the capillary conducted response is, at times, dependent upon the pannexin/purinergic- pathway making it potentially critical in the regulation of skeletal muscle blood flow.
URI: http://hdl.handle.net/10214/16716
Date: 2019-06
Rights: Attribution 4.0 International
Terms of Use: All items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.


Files in this item

Files Size Format View Description
Lamb_Iain_201907_PhD.pdf 1.872Mb PDF View/Open Lamb_Iain_201907_PhD

This item appears in the following Collection(s)

Show full item record

Attribution 4.0 International Except where otherwise noted, this item's license is described as Attribution 4.0 International