Interaction between sympathetic nerve activation and muscle fibre contraction in resistance vessels of hamster retractor muscle.

Competition between vasodilatation and vasoconstriction in skeletal muscle reflects a dynamic interaction between the local regulation of tissue blood flow and the autonomic neural regulation of arterial perfusion pressure (Folkow et al. 1971; Rowell, 1974). At rest, vasomotor tone is high throughout the resistance network. In response to muscle contraction, vasodilatation increases local blood flow and the supply of oxygen to active fibres (Gorczynski et al. 1978; Marshall & Tandon, 1984; VanTeeffelen & Segal, 2000). Initially, dilatation of distal arterioles augments capillary perfusion (Sweeney & Sarelius, 1989) and diffusional exchange between blood and tissue (Mellander, 1971). As the intensity of contractile activity and metabolic demand increase, greater total flow into the muscle is achieved through vasodilatation ascending progressively into the proximal arterioles and feed arteries (Folkow et al. 1971; Welsh & Segal, 1997; Segal & Jacobs, 2001). Sympathetic nerve activation (SNA) increases as a function of exercise intensity and with the mass of muscle engaged in contractile activity (Alam & Smirk, 1937; Seals, 1989). The interaction between functional vasodilatation and sympathetic vasoconstriction has long driven studies of blood flow control (Bulbring & Burn, 1939; Cobbold et al. 1963; Rowell, 1974; Granger et al. 1976), with controversial findings. On one hand, sympathetic vasoconstriction can restrict the increase in blood flow to exercising muscle (Strandell & Shepherd, 1967; Thompson & Mohrman, 1983; Buckwalter et al. 1997; O'Leary et al. 1997). On the other hand, vasoconstriction in response to SNA is impaired during muscle contractions (Remensnyder et al. 1962; Kjellmer, 1965; Burcher & Garlick, 1973; Richardson et al. 1995; Thomas et al. 1997). The controversy surrounding the ability of the vascular supply of skeletal muscle to undergo ‘functional sympatholysis' during exercise (Remensnyder et al. 1962) is underscored by variations in experimental design, data analyses and graphical presentation (Strandell & Shepherd, 1967; Thompson & Mohrman, 1983; O'Leary, 1991). Furthermore, the outcome of an experimental manipulation can be determined by changes in the initial baseline from which a response is evaluated (Myers & Honig, 1969). Therefore, to resolve how contractile activity can influence sympathetic vasoconstriction requires that responses to SNA also be evaluated when blood flow is elevated in resting muscle (Rowlands & Donald, 1968). Vasomotor responses to SNA have been well characterised in arterioles of resting skeletal muscle using intravital microscopy (Marshall, 1982; Fleming et al. 1987; Boegehold & Johnson, 1988b; Ohyanagi et al. 1991; Kurjiaka & Segal, 1995; Welsh & Segal, 1996). In contrast, few studies have investigated how arteriolar responses to SNA are influenced by muscle contraction (Dodd & Johnson, 1991, 1993). Moreover, there are no direct observations of how feed arteries (FA), which can present nearly half of the total resistance to muscle blood flow (Williams & Segal, 1993; Welsh & Segal, 1996), respond during interactions between muscle fibre contraction and SNA. Because blood flow through FA reflects the concerted response of the entire resistance network, observing the behaviour of these proximal vessels may provide key insight as to how SNA and muscle fibre contraction interact to determine the magnitude of muscle blood flow. Our goal in the present study was to evaluate the interaction of SNA and muscle fibre contraction on vasomotor responses of proximal though distal branches of the resistance network of skeletal muscle. The hamster retractor muscle preparation was used as model to enable direct observation of FA and arterioles under defined levels of tension production and SNA (Welsh & Segal, 1997; Jacobs & Segal, 2000; VanTeeffelen & Segal, 2000). We tested two hypotheses: (1) responses to SNA during muscle contraction would vary with vessel branch order; and (2) the interaction between SNA and muscle contraction would be influenced by respective levels of SNA and contractile activity. To evaluate how concerted network responses determined total flow into the muscle, red blood cell velocity (Vrbc) was measured together with diameter in FA. In complimentary experiments, vasodilators were administered to resting muscle to determine how a change in baseline per se can influence vasomotor responses to SNA, independently of muscle contraction.