Barbital-sedated, warm-acclimated (WA) or cold-acclimated (CA) rats were infused intravenously with noradrenaline (NA) at doses that elicited graded calorigenic responses. Blood flow (Q) to the various bodies of brown adipose tissue (BAT), the major sites of the NA-induced calorigenesis, was measured with labeled microspheres. The O2 content of arterial blood and of venous blood from interscapular BAT and the concentration of NA in arterial plasma (ANA) were also determined. ANA was linearly related to the dose of NA. Calorigenic response and the Q of total BAT and of separate bodies of BAT were sigmoid functions of ANA. The threshold for calorigenic response or for increased flow to BAT was an ANA of about 2 ng/mL (12 nM), except for some bodies of BAT in CA rats where it was closer in 4 ng/mL. Delivery of O2 to total BAT and calorigenic response were related linearly. The bodies of BAT were heterogeneous in Q per gram in CA rats the hierarchy in Q per gram changed markedly as ANA and calorigenic response increased. The analysis of these results takes into account that calorigenesis in BAT normally is not mediated by circulating NA, that in NA-infused rats neuronal and extraneuronal uptakes of NA would effect a lower concentration of NA at the adrenoceptors of BAT than in circulation, and that many factors such as organization and density of adrenergic innervation and the number of efficacy of receptors must have contributed to determining the measured responses of BAT. It is concluded that the differently located bodies of BAT in rats may have significant differences in composition and structure and that they may undergo differential development during cold acclimation.
The effects of sham, unilateral, and bilateral surgical denervation of rat interscapular brown adipose tissue (IBAT) on blood flow to the two IBAT pads of cold-acclimated (CA) rats during exposure of the animals to 22 or -6 degrees C and on the noradrenaline (NA) content and total dopamine beta-hydroxylase (DBH) (EC 1.14.17.1) activity of the pads in both warm-acclimated (WA)rats and CA rats were examined. Increase in IBAT blood flow upon cold exposure was taken as an index of sympathetically medicated calorigenesis in the tissue, and decreases in tissue levels of NA and DBH served as indices of the extent of destruction of the sympathetic innervation. At 24 h postsurgery, denervated pads of CA rats, rats, whether from unilaterally or bilaterally denervated IBAT, had less than 3% of the NA, 40-44% of the DBH, and 0% of the 10-fold, cold-induced increase in blood flow measured in intact pads of CA rats with sham-operated or unilaterally denervated IBAT. IBAT bilaterally denervated for 24 h was as responsive in terms of its maximum increase in blood flow during infusion of CA rats with NA as intact IBAT. DBH in denervated pads of both WA rats and CA rats fell to 5% or less of control levels at 2 days postdenervation and remained at these low levels, as did NA, for at least 8 weeks. These results strongly support the longstanding but recently challenged hypothesis that each pad of rat IBAT is independently innervated by sympathetic fibers.
The technique of using gamma-labeled plastic microspheres (15 +/- 5 micrometer) to measure cardiac output (CO) and its fractional distribution (FD) to individual tissues and organs was judged by various criteria to give valid data when applied to barbital-sedated warm-acclimated or cold-acclimated (CA) white rats, which were either resting or responding calorigenically to infused noradrenaline (NA). The FD of CO to each of 16 tissues or organs of CA rats at rest or responding to NA was then estimated both with 86Rb+ and with microspheres, the two tracers being injected simultaneously. For only seven of the tissues examined in resting rats and only one in NA-infused rats was the FD of CO estimated with 86Rb+ not significantly different from that estimated with microspheres. 86Rb+ to microsphere ratios of the FD of CO to individual tissues ranged from 3.5 and 3.0 for liver and skeletal muscle, respectively, down to 0.09 and 0.07 for brown adipose tissue (BAT) and brain. Since microsphere-based estimates of blood flow to the interscapular BAT of CA rats responding to NA were corroborated by direct measurements of venous efflux from the tissue, it is unequivocal that the 86Rb+-based estimate of the fraction of CO directed to interscapular BAT was highly erroneous. When considered along with data from the literature, the present findings support a conclusion that the uptake of 86Rb+ by a tissue frequently does not provide a valid measure of the FD of CO to the tissue. Some of the factors that are likely responsible for this situation are discussed, and it is suggested that only by a fortuitous combination of circumstances does the uptake of 86Rb+ by a tissue sometimes match the FD of CO to the tissue.
The rate of blood flow (Q) to interscapular brown adipose tissue (IBAT) and the arteriovenous difference in plasma noradrenaline (NA) across the tissue were measured in warm-acclimated (WA) or cold-acclimated (CA) rats during infusion of NA at doses of 1-12.5 ng min-1 g-0.74 (approximately 0.2-2.7 micrograms min-1 kg-1) and in the period of steady calorigenic response associated with steady concentration of NA in arterial plasma (ANA). ANA was linearly related to the dose of NA. Calorigenic response, percentage of cardiac output to IBAT, and Q per gram of IBAT were sigmoid functions of ANA and at their maxima were about 2.5 times greater in CA than in WA rats. The rate of uptake of NA by IBAT increased with ANA and Q, each of which had a major influence on rate, but the coefficient of extraction of NA by the tissue (ENAIBAT) declined. Measurements in rats given a dose of propranolol that partially inhibited the NA-induced increase in Q to IBAT indicated that the decline in ENAIBAT was attributable primarily to the increase in Q rather than to increasing saturation of uptake mechanisms. Diffusion-limited extraction of NA is the probable basis for the effect of Q on ENAIBAT. Possible implications of flow-dependent extraction of NA in studies involving measurements of the uptake of exogenous NA by tissues or organs are discussed.
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