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 signalling 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 (CVD) encompasses greater distances than can be explained by passive decay and understanding such behaviour 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. CVD is tempered by sympathetic neuroeffector signalling when governing muscle blood flow at rest and during exercise. Impairment of conduction during ageing and in diseased states can limit physical work capacity by restricting muscle blood flow.

Figure 1. Ascending vasodilation in a resistance network controlling blood flow to skeletal muscle

(a) Depiction (not to scale) of conduit artery and vein giving rise to feed artery (FA) and collecting vein (CV). Once the FA branch enters skeletal muscle it gives rise to first-order (1A), second-order (2A), third-order (3A) and terminal (TA) arterioles shown in black. A capillary network (cap) arises from the TA and converges into venules shown in parallel (gray) to arterioles. (b) Vasodilation originating from TA and 3A ascends into proximal 2A (arrow), contributing to an increase in local blood flow and capillary red cell perfusion. (c) Vasodilation ascends from intramuscular arterioles into the FA external to the muscle, contributing to an increase in total blood flow entering the muscle.

Figure 2. Initiation and conduction of vasodilation

Depiction of longitudinal section of arteriolar wall (top) with endothelial cells in gray and smooth muscle cells in white (not to scale). The internal elastic lamina located between respective cell layers is omitted for clarity. (a) Integrated schematic depicting the initiation and conduction of hyperpolarization and vasodilation. Labels 1, 2, and 3 correspond to events shown with greater detail in respective components of panel (b). Hyperpolarization (-) is conducted along ECs (shaded with horizontal arrows) and into consecutive SMCs (vertical arrows). (b) Details of respective events indicated in upper panel. 1: Binding of ACh to a muscarinic receptor (M) triggers production of inositol 1,4,5-trisphosphate (IP₃) in the cytoplasm which binds to its receptor (IP₃R), releasing Ca²⁺ from the endoplasmic reticulum to stimulate Ca²⁺-activated potassium channels (K_Ca) in the plasma membrane. The efflux of K⁺ produces hyperpolarization which is conducted from EC to EC through homocellular gap junctions (GJ). 2: Along the vessel wall, hyperpolarization travels through myoendothelial gap junctions (MEGJ) to hyperpolarize SMCs and cause vasodilation by closing voltage gated Ca²⁺ channels (VGCC) to reduce Ca²⁺ entry. 3: The conduction of hyperpolarization can be augmented through activation of inward rectifying K⁺ channels (K_IR), which may also occur along the endothelium (not depicted).