Oxygen uptake and tissue oxygen tension during adrenergic stimulation in canine subcutaneous adipose tissue.

The effect of sympathetic nerve stimulation (NS) and injected noradenaline (NA) or isoprenaline (Iso) on PVO2, VO2 and PtO2 was studied in isolated canine subcutaneous adipose tissue. These effects were compared to those produced by mechanical blood flow reduction (clamping). Resting VO2 measured 13.0+/- 2.3 mumol X min-1 X 100 g-1. When blood flow was reduced by 20% or less there was no significant change of VO2. Reducing blood flow to 50% of control or less by NS caused a parallel reduction in VO2, while clamping reduced VO2 significantly less. NA gave effects similar to those of NS. After NS or NA there was a period of hyperemia and increased oxygen extraction which more than compensated for the decrease in VO2 during vasoconstriction. Such a net increase in VO2 was not produced by clamping. Control PtO2 averaged 29+/-2 mmHg. NA reduced it by 70% and clamping to the same blood flow level only by 14% (p less than 0.01). Thus, a mere reduction in blood flow has little effect on PtO2, while blood flow reduction combined with redistribution of blood flow and an increased oxygen deman can lead to tissue hypoxia.     

Regulation of sympathetic nerve activity by L-carnosine in mammalian white adipose tissue

Previously, we showed that l-carnosine, a bioactive dipeptide, influences the sympathetic nerve activity innervating kidney and brown adipose tissue. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of L-carnosine on the sympathetic nerve activity innervating white adipose tissue (SNA-WAT) and lipolysis. We found that intraperitoneal (ip) administration of L-carnosine at doses of 100 ng/rat and 10 microg/rat elevated and suppressed SNA-WAT, respectively. The effect of lower dose of L-carnosine (100 ng/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of higher dose of L-carnosine (10 microg/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, ip administration of 100 ng and 10 microg of L-carnosine increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The changes of plasma FFAs resulting from the exposure to 100 ng and 10 microg of L-carnosine were diminished by the beta-adrenergic receptor blocker propranolol hydrochloride and the muscarinic receptor blocker atropine sulfate, respectively; and eliminated by the corresponding histamine receptor antagonists, which eliminated the changes in SNA-WAT. Our results suggest that low doses of L-carnosine may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H(1) receptor, and that the beta(3)-receptor may be involved in this enhanced lipolytic response. High doses of L-carnosine, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H(3) receptor, and the muscarinic receptor may be related to this response.     

Changes in ATP and cyclic nucleotide levels during sympathetic nerve stimulation in canine subcutaneous adipose tissue in situ.

Subcutaneous adipose tissue in fed, female dogs was isolated. Biopsies of the tissue (30-150 mg) were taken and rapidly frozen in liquid nitrogen before, during and after nerve stimulation (3-4 Hz). In unstimulated adipose tissue the levels of ATP1 were 74+/-7 nmol/g, of cyclic AMP 90 +/- 12 pmol/g and of cyclic PGMP 18 +/- 3 pmol/g (mean+/-S.E.). During sympathetic nerve stimulation the levels of ATP and cyclic GMP fell by 30 and 50% respectively (p less than 0.01), while the cyclic AMP content increased by 50% (p less than 0.05). After nerve stimulation there was a marked increase in glycerol release, and the levels of all three nucleotides returned to control. The fall in ATP during nerve stimulation was essentially eliminated by prior adrenergic alpha-receptor blockade. It is concluded that 1) sympathetic nerve stimulaton induces a rapid, reversible fall in tissue ATP content, which may be related to hypoxia secondary to the vasoconstriction, and 2) lipolytic responses to sympathetic nerve stimulation in vivo are preceeded by small increases in the tissue cyclic AMP level, and a 3-fold increase in the cyclic AMP/cyclic GMP ratio.     

Influence of adenosine on the vascular responses to sympathetic nerve stimulation in the canine subcutaneous adipose tissue

Adenosine appears to regulate resting blood flow in canine subcutaneous adipose tissue. Sympathetic nerve stimulation has been shown to enhance the adenosine production in this tissue. This study therefore tested the possibility that adenosine may influence the vascular responses to sympathetic nerve stimulation. Intraarterial infusion of adenosine (5–20 μM in arterial blood) increased the resting vascular conductance (from 0.048 ± 0.007 to 0.095 ± 0.013 ml ± min^-1100 g^-1± mmHg^-1) and the percental reduction in vascular conductance due to sympathetic nerve stimulation (4 Hz) by 34 per cent (p<0.05) and to i. a.noradrenaline by 27 per cent (p<0.05). The vasodilator response due to nerve stimulation after α-blockade was reduced by adenosine. Dipyridamole (0.5–1.5 μM) + EHNA (3–10 μM), which increases plasma adenosine levels, had similar effects to adenosine, while theophylline (30–80 μM) decreased the vasoconstrictor response. The vasoconstrictor escape was enhanced by EHNA alone and in combination with dipyridamole, but was reduced by theophylline. On the other hand, the poststimulatory hyperemia was unaffected by adenosine, dipyridamole and EHNA, and theophylline. The results show that adenosine does not reduce the magnitude of the initial vasoconstrictor response in proportion to the increase in resting blood flow. The autoregulatory escape in adipose tissue during nerve stimulation appears to be mediated both by adenosine and by noradrenaline acting on β-adrenoceptors. Poststimulatory hyperemia does not seem to be greatly influenced by exogenous or endogenous adenosine     

Release of noradrenaline from the cat spleen by nerve stimulation and potassium.

1. In rabbits under pentobarbitone anaesthesia stimulation of the nasal mucous membrane with ether vapour causes apnoea, bradycardia and a rise in arterial blood pressure. 2. Simultaneous measurements of femoral arterial blood pressure and of femoral arterial or venous blood flow show that vascular resistance increases in both the intact and skinned hind limb in response to nasal stimulation. Evidence is presented to show that the increase in hind-limb vascular resistance is due to vasoconstriction which is relfex in nature. 3. The change in vascular resistance in the hind limb following nasal stimulation may be divided into two distinct phases. The primary (early) phase is mediated by the efferent sympathetic nerves to the limb whereas the secondary (late) phase is mediated by adrenal gland hormones. 4. The secondary phase of the hind-limb vascular response is invariably less pronounced than the primary phase, and with regard to the time course of the appearance of the two phases of the response it appears that following stimulation of the nose there is no mutual reinforcement of sympathetic neural and humoral influences on the hind-limb blood vessels. 5. The cardiovascular response occur in the absence of changes in pulmonary ventilation.     

Release of noradrenaline by splenic nerve stimulation and its dependence on calcium

1. Cat spleens were perfused with Krebs bicarbonate solution using a constant flow pump. The amount of noradrenaline released during splenic nerve stimulation was measured at various frequencies. The dependence of noradrenaline release on the ionic composition of perfusion medium was also determined.2. The effect of frequency of stimulation on the output of noradrenaline was studied in both normal and phenoxybenzamine treated cats. In normal cats, the output was 0.33 ng/stimulus at 10/sec, whereas it was 1.21 ng/stimulus at 30/sec. In phenoxybenzamine-treated cats, the maximum output of noradrenaline of 4 ng/stimulus was obtained at 5 or 10/sec. Higher or lower frequencies of stimulation produced lower output.3. In both normal and phenoxybenzamine treated cats, removal of calcium from the perfusing medium nearly abolished the release of noradrenaline in response to nerve stimulation. Replacement of calcium restored the noradrenaline release. The noradrenaline output/stimulus was linearly related to the log of the external calcium concentration.4. Increasing the concentration of magnesium to (10-20 mM) reduced the noradrenaline output. This depressant effect of magnesium was partially antagonized by increasing the calcium concentration of the perfusion solution.5. Divalent alkali metal earths such as barium and strontium were able to substitute for calcium. Barium substitution nearly doubled the noradrenaline output/stimulus and increased the pressor activity of the samples taken just before nerve stimulation.6. Removal of potassium from the perfusion fluid or lowering the sodium concentration to 50 mM had little effect on the release of noradrenaline. Lowering the sodium concentration to 37.5 mM or less usually abolished the noradrenaline output; this effect is attributed to blockade of nerve conduction.7. It is suggested that depolarization of post-ganglionic sympathetic nerve terminals may increase the influx of calcium ions which in turn leads to the release of noradrenaline from the nerve terminals.