Metabolic‐vascular coupling in skeletal muscle: A potential role for capillary pericytes?

Abstract

The matching of capillary blood flow to metabolic rate of the cells within organs and tissues is a critical microvascular function which ensures appropriate delivery of hormones and nutrients, and the removal of waste products. This relationship is particularly important in tissues where local metabolism, and hence capillary blood flow, must be regulated to avoid a mismatch between nutrient demand and supply that would compromise normal function. The consequences of a mismatch in microvascular blood flow and metabolism are acutely apparent in the brain and heart, where a sudden cessation of blood flow, for example following an embolism, acutely manifests as stroke or myocardial infarction. Even in more resilient tissues such as skeletal muscle, a short-term mismatch reduces muscle performance and exercise tolerance, and can cause intermittent claudication. In the longer-term, a microvascular-metabolic mismatch in skeletal muscle reduces insulin-mediated muscle glucose uptake, leading to disturbances in whole-body metabolic homeostasis. While the notion that capillary blood flow is fine-tuned to meet cellular metabolism is well accepted, the mechanisms that control this function and where and how different parts of the vascular tree contribute to capillary blood flow regulation remain poorly understood. Here, we discuss the emerging evidence implicating pericytes, mural cells that surround capillaries, as key mediators that match tissue metabolic demand with adequate capillary blood flow in a number of organs, including skeletal muscle. K E Y W O R D Scapillary blood flow, microvasculature, pericytes, skeletal muscle | 521 ATTRILL eT AL.

August Krogh's theory of muscle microvascular control and oxygen delivery: a paradigm shift based on new data

“…More recently, the potential of cardiac pericytes to constrict during hypoperfusion and ischaemia (Methner et al 2019;O'Farrell et al 2017) has been considered. However, despite over a century of investigation and conjecture (Attrill et al 2019) no definitive role for pericytes in matching O 2 delivery to O 2 uptake (i.e.Q O 2 tȯ V O 2 ) in skeletal muscle has been resolved.…”

“…However, despite over a century of investigation and conjecture (Attrill et al . 2019) no definitive role for pericytes in matching O 2 delivery to O 2 uptake (i.e. to ) in skeletal muscle has been resolved.…”

The coronary capillary bed and its role in blood flow and oxygen delivery: A review

“…In transgenic mice with partial pericyte depletion, the number of capillary segments that constricted was only 14% compared to a 33% capillary segment number in wild-type littermate controls. These data support selective flow regulation in the capillary bed, via diameter changes and implicate pericytes as key mediators that facilitate metabolic demand with capillary blood flow in several organs, especially skeletal muscle (reviewed by Attrill et al, 2020).…”

The role of pannexin/purinergic signaling in intervascular communication from capillaries during skeletal muscle contraction in male Golden hamsters

“…Pericytes are found at the capillary level in skeletal muscle, yet their function remains poorly understood (for review see Murray et al, 2017). The population of pericytes associated with the skeletal muscle vasculature is not well defined, where the coverage has been estimated as low as 1:100 pericyte to endothelial cells (Diaz-Flores et al, 2009;Shepro & Morel, 1993) to extensive pericyte coverage of skeletal muscle capillaries reported in a more recent study (Attrill et al, 2020). If pericytes form a continuous layer on capillaries and share the same capillary unit structure, there is the possibility they may play a role in signal transmission along the vasculature.…”