Microsphere infusion reverses vasoconstrictor-mediated changes in hindlimb oxygen uptake and energy status

The vasoconstrictors, angiotensin II (AII) and serotonin (5-HT) produce opposing metabolic effects and appear to control different flow routes in the constant-flow perfused rat hindlimb. In the present study the association between vascular flow route recruitment and metabolism was assessed by selective microsphere embolism of either route. Microspheres (MS, 11.9 ± 0.1 μm, mean ± SE diameter) were injected during AII, 5-HT or vehicle infusions (basal conditions) and the effects on hindlimb (4.7 ± 0.1 g muscle) oxygen uptake (V̇O2) and indices of energy status CrP/Cr, CrP/ATP and energy charge (EC) of the calf muscle group assessed. MS (1.5 x 106) injected during vehicle, or 5-HT infusion increased V̇O2 (P < 0.05) but did not affect energy status. During AII, MS decreased V̇O2. Change in V̇O2 correlated positively with CrP/Cr (r = 0.68, P < 0.0001) and CrP/ATP (r = 0.51, P < 0.001) but not EC (r = 0.08, P = 0.59). MS (1.5 x 106) increased pressure but did not affect the flow rate. The metabolic changes resulting from 1.5 x 106 microspheres were intensified by a second injection of 1.5 x 106 microspheres but further injection (>3.0 x 106 microspheres) began to inhibit flow. It is concluded that a finite number (≤3.0 x 106) of microspheres of 11.9 μm diameter has opposite effects on V̇O2 depending on the vasoconstrictor present and that these effects result from the occlusion of the different vascular route accessed by each vasoconstrictor. The data support the proposal that hindlimb metabolism can be controlled by vasoconstrictors as a result of selective vascular recruitment.