Norepinephrine and serotonin vasoconstriction in rat hindlimb control different vascular flow routes

Abstract

The vasoconstrictors, norepinephrine at low dose ( < or = 0.1 microM; LDNE) and serotonin (5-HT), produce opposing metabolic effects in the constant-flow perfused rat hindlimb characterized by increased and decreased oxygen uptake, respectively. In the present study, the effects of each vasoconstrictor are compared in the red blood cell-free buffer-perfused hindlimb on postequilibration endogenous red blood cell efflux, vascular entrapment of fluorescein-labeled dextran (Fx), and vascular corrosion casting by use of 30-micron spheres of methyl methacrylate (MM). A marked transient washout of red blood cells occurred immediately in association with vasoconstriction induced by LDNE that was not apparent when a similar extent of vasoconstriction was induced by 5-HT. Fx perfusions indicated that LDNE recruited a new vascular space that was reaccessed by a second exposure to the vasoconstrictor. 5-HT closed off a previously perfused vascular space that was reaccessed when the vasoconstrictor was removed. Corrosion casting of the arterial tree with MM showed no increase in cast weight, but more vessels filled because of LDNE. Higher doses of NE (2.5 microM) or 5-HT caused a marked decrease in cast weight with fewer vessels filled. The data suggest that LDNE and 5-HT, in association with vasoconstriction at different sites, control different capillary flow routes in the hindlimb that in turn may influence metabolism by increasing or decreasing nutrient access, respectively.

Nonnutritive flow impairs uptake of fatty acid by white muscles of the perfused rat hindlimb

“…Physical evidence for the concept of two vascular routes in muscle comes from a number of studies that we have undertaken and includes vascular casting (21), FITC-dextran entrapment as a marker for recruited and derecruited vascular space (21), surface fluorescence measurement of tendon vessels when perfused with a fluorescent vascular marker (22), microdialysis out-to-in ratio of 3 (5), and microsphere embolism with use of latex microspheres of different sizes (38). However, the precise anatomic nature of the nonnutritive route of muscle is still unresolved, despite knowledge of its presence for 70 years (24).…”

Graded occlusion of perfused rat muscle vasculature decreases insulin action

“…30-34 % [32]. Using a number of approaches, including vascular casting [26], red blood cell washout [26], fluorescent dextran entrapment [26] and microscopic visualization [33], it appears likely that 5-HT vasoconstricts in regions of the vasculature to redirect flow to a non-nutritive route that occurs predominantly in connective tissue, closely associated with the muscle fibres (e.g. see [34] and references therein).…”

“…The concept of non-nutritive vessels distributed throughout the load-bearing muscles of the limbs is not new, and proposals that they also occur in connective tissue date back at least 40 years [35]. Whatever their intrinsic nature, the non-nutritive vessels are capillarylike, as they do not readily pass MS of 12-15 µm in diameter [26,36]. When flow is carried by these nonnutritive vessels, oxygen delivery, in terms of availability for mitochondrial oxidative metabolism, is reduced.…”

“…AngII recruits and 5-HT de-recruits nutritive flow by vasoconstriction [20], presumably by acting at different sites in the hindlimb vasculature [26]. Figure 3 shows the representative time course traces from perfusions involving the introduction of 30 × 10 6 MS or vehicle bolus alone.…”

Na+channel and Na+-K+ATPase involvement in norepinephrine- and veratridine-stimulated metabolism in perfused rat hind limb

“…A key element of the indirect vascular mechanism appears to be the redistribution of flow between two distinct vascular pathways within muscle . Evidence includes the vasoconstrictormediated washout of red blood cells from the perfused tissue, even after a suitable equilibration period (Newman et al 1996). In addition, fluorescent dextran (M r 150 000) studies showed that this marker was entrapped in a new vascular space accessed by low-dose norepinephrine (LDNE) (Newman et al 1996).…”