In the resting state, tissue blood flow is limited by the resistance of small arteries and arterioles. Thus, dilation of resistance vessels is a prerequisite to increasing tissue perfusion during metabolic activity. Vasodilation localized to a single region of a vessel will have little effect on tissue blood flow. It is therefore necessary to utilize a mechanism that enables vasomotor responses to affect entire segments and regions of vascular networks. In active tissues, such as contracting skeletal muscle, arterioles within the tissue dilate, and this vasodilation “ascends” into upstream feed arteries via cell-to-cell conduction. This ascending vasodilation reduces total resistance to flow for vessels connected in series and parallel, and is a key component of increasing tissue blood flow.
Cell-to-cell conduction of vasomotor responses reflects the spread of electrical signals through the cells of the vessel wall via gap junctions. A preparation that has been developed to investigate these relationships is the feed artery to the hamster retractor muscle. In these vessels studied in vitro, the neurotransmitter ACh initiates a conducted hyperpolarization and vasodilation, and therefore mimics the actions of the metabolites released by active tissues. The ion channels that initiate this response remain unclear, although evidence from related studies suggests involvement of the Kca. While the electromechanical response mediates the onset and magnitude of CVD, studies have suggested that an autacoid-mediated component sustains the response. The mechanisms involved in this component of CVD remain unclear, as changes in endothelial cell Ca2+ (a major physiological trigger for autacoid production) have not been resolved, particularly during the conducted vasomotor response. It is therefore necessary to employ modern imaging techniques with improved Ca2+ indicators to fully understand the Ca2+ dynamics during CVD. The second Aim of my thesis relies on these techniques to define a novel, Ca2+-mediated signaling pathway that complements the more widely recognized electrical signaling pathway.