Size-Dependent Effects of Microspheres on Vasoconstrictor-Mediated Change in Oxygen Uptake by Perfused Rat Hindlimb

Abstract

There are two vascular flow routes in skeletal muscle that can be accessed by different vasoconstrictors acting at selective sites in the vascular tree. Thus, angiotensin II (AII) and serotonin (5-HT), which stimulate and inhibit metabolism, do so by directing flow to nutritive and nonnutritive routes, respectively. In the present study the association between vascular flow route recruitment and metabolism was assessed by embolism with microspheres of different sizes. Latex microspheres (MS) of four sizes, 5.4 (MS5), 11.8 (MS12), 23.4 (MS23), and 93.6 μm (MS94), were injected during AII- or 5-HT-mediated constriction or under basal conditions and the effects on hindlimb oxygen uptake (V̇O₂), perfusion pressure, and venous flow rate were determined. MS5 or MS12 partially reversed 5-HT-mediated inhibition of V̇O₂ by 39 and 55%, respectively (P < 0.05), fully reversed AII-mediated stimulation of V̇O₂ (P < 0.05), stimulated basal V̇O₂ (P < 0.05), and increased pressure while only marginally (<10%) decreasing venous flow. MS23 or MS94 dose-dependently increased pressure and inhibited V̇O₂, during basal or 5HT- and AII-mediated constriction, while only marginally decreasing venous flow. In conclusion, microspheres of less than 12 μm when injected into the constant flow perfused rat hindlimb can alter metabolism by altering flow distribution between nutritive and nonnutritive routes. Larger MS (≥24 μm) are nondiscriminating possibly because they exceed the size of vessels in which branch points to the two vascular routes are located. Overall the findings provide further evidence for two microvascular routes in muscle, one nutritive and the other nonnutritive.