Attenuation of vasodilatation with skeletal muscle fatigue in hamster retractor.

Muscle blood flow increases in response to rhythmic contractions, achieving a steady state of functional hyperaemia that is proportional to the tension produced and/or the frequency of contractions (Anrep & Von Saalfeld, 1935; Fales et al. 1960; Hudlicka, 1973; Laughlin & Armstrong, 1982; Andersen & Saltin, 1985; Armstrong et al. 1987). Increases in muscle blood flow are governed by vasodilatation throughout the resistance network. As muscular work intensifies, the locus of vasomotor control ascends from the smallest, distal arterioles into larger, proximal arterioles and the arterial supply (Hilton, 1959; Goodman et al. 1978; Honig et al. 1980; Klitzman et al. 1982; Williams & Segal, 1993; Welsh & Segal, 1997). Upon cessation of contraction, the elevation in blood flow returns to resting levels during a period of post-contraction hyperaemia that is also proportional to the preceding level of activity (Hilton, 1953; Dornhorst & Whelan, 1953; Khayutin, 1968). Functional vasodilatation has long been argued to explain the proportionality between the activity (e.g. tension production) of muscle fibres and the magnitude of skeletal muscle blood flow (Gaskell, 1877; Shepherd, 1983). According to the metabolic theory of blood flow regulation, vasoactive metabolites are released from muscle fibres in proportion to their activity and diffuse to relax vascular smooth muscle cells. This ‘metabolic vasodilatation’ increases the supply of oxygen and nutrients in response to tissue demand (Hudlicka, 1973; Haddy & Scott, 1975; Sparks, 1980). While such behaviour has been documented with intravital microscopy in the cremaster (Gorczynski et al. 1978; Klitzman et al. 1982) and spinotrapezius (Marshall & Tandon, 1984) muscles, little is known of how changes in the ability to produce tension and generate metabolites may influence the hyperaemic response to muscle contraction. During fatigue, contractile function is impaired (Merton, 1954; Edwards et al. 1977; Fitts, 1994). Consequently, metabolic rate (e.g. ATP turnover, glycogenolysis; oxygen consumption) is attenuated (Dawson et al. 1978; Edwards, 1981). This behaviour suggests that the production of vasoactive stimuli may decline as a muscle fatigues, though the relationship between contractile function and vasodilator production may not be linear. Muscle blood flow and tension production have been studied in relation to fatigue (Barclay, 1986; Bark et al. 1987; Supinski et al. 1993; Ameredes et al. 1994). However, there is a paucity of information concerning the effect of muscle fatigue on vasomotor tone or the reactivity of resistance vessels to contractile activity. Changes in the interstitial milieu (e.g. metabolites) that are associated with muscle fatigue (Edwards, 1981; Supinski et al. 1988) may also affect the resting state and/or the responsiveness of the vascular supply. In the present study, we utilized the hamster retractor muscle preparation (Nakao & Segal, 1995; Welsh & Segal, 1996) to investigate the effect of muscle fatigue on the behaviour of arterioles and feed arteries that control blood flow to active muscle fibres. We hypothesized that, if the regulation of muscle blood flow is in accord with the metabolic theory, then vasodilator responses to contraction should be attenuated as tension production (and metabolic demand) are diminished with fatigue. Responses were evaluated throughout the resistance network to further determine whether the locus and time course of blood flow control were altered by muscle fatigue.