Regulation of blood flow in the microcirculation: role of conducted vasodilation

Abstract

This review is concerned with understanding how vasodilation initiated from local sites in the tissue can spread to encompass multiple branches of the resistance vasculature. Within tissues, arteriolar networks control the distribution and magnitude of capillary perfusion. Vasodilation arising from the microcirculation can 'ascend' into feed arteries that control blood flow into arteriolar networks. Thus distal segments of the resistance network signal proximal segments to dilate and thereby increase total oxygen supply to parenchymal cells. August Krogh proposed that innervation of capillaries provided the mechanism for a spreading vasodilatory response. With greater understanding of the ultrastructural organization of resistance networks, an alternative explanation has emerged: Electrical signaling from cell to cell along the vessel wall through gap junctions. Hyperpolarization originates from ion channel activation at the site of stimulation with the endothelium serving as the predominant cellular pathway for signal conduction along the vessel wall. As hyperpolarization travels, it is transmitted into surrounding smooth muscle cells through myoendothelial coupling to promote relaxation. Conducted vasodilation encompasses greater distances than can be explained by passive decay and understanding such behavior is the focus of current research efforts. In the context of athletic performance, the ability of vasodilation to ascend into feed arteries is essential to achieving peak levels of muscle blood flow. Conducted vasodilation is tempered by sympathetic neuroeffector signaling when governing muscle blood flow at rest and during exercise. Impairment of conduction during aging and in diseased states can limit physical work capacity by restricting muscle blood flow.

The Mouse Cremaster Muscle Preparation for Intravital Imaging of the Microcirculation

“…The orchiectomy serves to avoid possible trauma to the tissue when pushing the testes back into the abdominal cavity. We have not found noticeable differences in the quality of the cremaster microcirculation preparation (see Section 3.8) using either procedure 7,15 . 6.…”

Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca 2+ events, and IK Ca channels, reducing arteriolar tone

“…The inverse relationship between EC Ca 2+ events and intraluminal pressure, and the fact this change persists at steady-state, suggests that reducing intraluminal pressure will cause vasodilation in myogenically active arteries/arterioles and sustain tissue blood flow. For example, when systemic blood pressure decreases or if local ischemia or an upstream stenosis drops arteriolar pressure, EC Ca 2+ events will generate hyperpolarization and give rise to conducted dilation (1,2). This vascular coordination involves electrical coupling via homo-and heterocellular gap junctions to sustain the spread of hyperpolarization through the endothelium.…”

“…This hyperpolarization spreads both radially and longitudinally through the vascular wall via patent gap junctions to evoke local and conducted dilation, and it is central to cardiovascular function (1,2).…”

Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

“…It is now well established that in the brain vascular responses propagate outward from their site of initiation [23], similar to what has been observed in the periphery [22]. The cells propagating this signal may vary, depending on the strength of stimulation, with evidence supporting signal propagation along both the vascular endothelium [58] and through the astrocytic syncytium [59].…”

“…Vascular responses propagate outward from their site of initiation [22,23], which means that late BOLD responses are less spatially localized to the initial site of neuronal activity than the first few seconds of the positive BOLD response (discussed below, and by Uhlirova et al [4] in this issue and in [24]). …”