Release of Adenosine-like Material from Isolated Perfused Dog Adipose Tissue Following Sympathetic Nerve Stimulation and its Inhibition by Adrenergic α-Receptor Blockade

Following the intraarterial infusion of ^sH-adenine to isolated perfused canine subcutaneous adipose tissue, its adenine nucleotides are labelled. A continuous release of radioactivity, comprised of non-nucleotide material, was observed. The rate of this release was markedly enhanced by sympathetic nerve stimulation. The major components of the enhanced release appeared to be inosine and adenosine. Adrenergic α-receptor blockade (phentolamine or Hydergin®) abolished the enhanced nucleoside release, while glycerol release was enhanced. The release of radioactivity was decreased during mechanical blood flow reduction and enhanced afterwards. However, the magnitude of this enhancement of release after clamp was much less than following nerve stimulation. The results suggest that adenosine or a closely related compound is released from canine subcutaneous adipose tissue by sympathetic nerve stimulation and that the release is related to adrenergic α-receptor stimulation. Since adenosine is a potent inhibitor of catecholamine induced lipolysis in this tissue the possibility of a regulatory role must be considered.     

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     

Effects of Prostaglandin E1 in Canine Subcutaneous Adipose Tissue in Situ1

The effect of PGE₁ on the uptake of glucose and the release of FFA and glycerol before and after sympathetic nerve stimulation (4 cps) was investigated in perfused canine subcutaneous adipose tissue in situ. Glucose uptake was significantly increased by PGE₁ at all concentrations used (5 times 10^-10 to 7 times 10^-7 M in blood). The effect of PGE₁ on the release of FFA and glycerol in unstimulated adipose tissue was inconsistent. Increases as well as decreases were observed. Lipolysis, as measured by glycerol release, induced by nerve stimulation was inhibited dose-dependently. A 50 per cent inhibition was produced by approximately 1.2 times 10^-7 M PGE₁. Stimulated FFA release was also inhibited but there was no clear dose-response relationship. It is concluded that PGE₁ has similar effects in canine subcutaneous adipose tissue with an intact blood supply as are known to be produced in vitro.     

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.     

The antilipolytic effect of endogenous and exogenous adenosine in canine adipose tissue in situ

The effects of adenosine, 2-Cl-adenosine, two adenosine uptake inhibitors (dipyridamole and dilazep) and the adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) were studied on basal and stimulated lipolysis in subcutaneous adipose tissue. The basal lipolysis was unaffected by all agents. Lipolysis induced by nerve stimulation (4 Hz, 5 min) was dose-dependently antagonized (up to 100%) by close i.a. infusions of adenosine (1–40 μM in blood); if the nerve induced vasoconstriction was prevented by α-adrenoceptor-blockade. 2-Cl-adenosine was a more potent antilipolytic agent than adenosine. EHNA (3–10 μM in blood) did not inhibit stimulated lipolysis in vivo possibly because of the low ADA activity in fat cells. Dipyridamole (0.5-1.5 μM in blood) in combination with EHNA increased the venous plasma concentration of adenosine from 0.3±0.05 to 0.7±0.1 μM and enhanced the tissue concentration close to 3-fold. Lipolysis induced by nerve stimulation (4 Hz) was reduced by about 40% by dipyridamole + EHNA and that induced by close i.a. noradrenaline injection (20 nmol) by approximately 60%. It is concluded that adenosine is an antagonist of stimulated lipolysis in subcutaneous adipose tissue in situ in concentrations that are reached during prolonged sympathetic nerve stimulation.     

Vascular and Metabolic Effects of Theophylline,Dibuturyl Cyclic AMP and Dibuturyl Cyclic GMP in Canine Subcutaneous Adipose Tissue in situ1

In canine subcutaneous adipose tissue theophylline (2×10^--⁴ M), cAMP and ATP (10^--⁵ M), and DBcAMP (8×10^--⁴ M) increased blood flow by by approximately 100 per cent. These compounds also antagonized sympathetic vasoconstriction. Theophylline and DBcAMP increased glycerol release dose-dependently, while cAMP and ATP were ineffective up to I mM. Theophylline (0.4–0.8 mM) potentiated the lipolytic effect of nerve stimulation, while 2–8 mM apparently caused maximal stimulation Per se. DBcAMP did not affect FFA release following nerve stimulation, while DBcGMP potentiated. The apparent rate of re-esterification, glucose uptake and lactate release was decreased by theophylline. DBcAMP (0.1–0.4 mM) had no effect on these parameters, while DBcGMP at the same concentration decreased re-esterification and lactate release. Stimulated overflow of ³H from tissues prelabelled with L-³H-noradrenaline was reduced to 50 per cent by ATP (0.1–0.4 mM), but was unaffected by DBcAMP and DBcGMP at the same concentration. The results support the view that cAMP mediates the metabolic actions of sympathetic nerve stimulation in canine subcutaneous adipose tissue. The relationship between cAMP and vascular reactions may be more complex.     

Fate of 3H-Noradrenaline in Canine Subcutaneous Adipose Tissue1

Canine subcutaneous adipose tissue was isolated and perfused with defibrinated blood at a constant rate. Infused ³H-noradrenaline was taken up by the tissue and released spontaneously into blood. Following a washout period of 40 min or more, plasma samples were withdrawn. Radioactive compounds in venous plasma were separated by chromatography on alumina and Dowex. About 30 per cent of the venous radioactivity was identified as unchanged noradrenaline, about 7 per cent as normetanephrine and 14 per cent as deaminated catechols: deaminated O-methylated metabolites accounted for about 45 per cent. This indicates the presence in adipose tissue of both monoamineoxidase and catechol-O-methyl-transferase. Upon stimulation of sympathetic nerves to adipose tissue peripheral resistance increased, the ³H-presence in adipose tissue of both monoamine oxidase and catechol-O-methyl-transferase. Upon cessation of the stimulation the peripheral resistance decreased and the outflow of noradrenaline metabolites increased above control values. After dihydroergotamine, nerve stimulation induced a decreased peripheral resistance, an increase of ³H-noradrenaline outflow and no change or an increase in the outflow of noradrenaline metabolites. Totally more radioactivity was released upon nerve stimulation after dihydroergotamine. The changes seen are interpreted to be associated with vascular reactions in adipose tissue.     

Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle

Sympathetic nerve stimulation (2 min, 2 and 10 Hz) increased perfusion pressure in the blood perfused canine gracilis muscle in situ after pretreatment with atropine, desipramine and beta-adrenoceptor antagonists. This vasoconstriction was accompanied by clear-cut increases in the overflow of endogenous noradrenaline (NA) at both frequencies and, at 10 Hz but not at 2 Hz, also of neuropeptide Y-like immunoreactivity (NPY-LI). The irreversible alpha-adrenoceptor antagonist phenoxybenzamine enhanced the nerve stimulation induced overflows of NA and NPY-LI five- to eightfold and threefold, respectively. The fractional overflows of NA and NPY-LI per nerve impulse were similar in response to the high-frequency stimulation, indicating equimolar release in relation to the tissue contents of the respective neurotransmitter. The maximal vasoconstrictor response elicited by 10 Hz was reduced by about 50% following a dose of phenoxybenzamine which abolished the effect of exogenous NA and the remaining response was more long-lasting. Local i.a. infusion of NPY evoked long-lasting vasoconstriction in the presence of phenoxybenzamine, while the stable adenosine 5(1)-triphosphate (ATP) analogue alpha-beta-methylene ATP was without vascular effects. Locally infused NPY reduced the nerve stimulation evoked NA overflow by 31% (P less than 0.01) at 1 microM in arterial plasma, suggesting prejunctional inhibition of NA release. In conclusion, NPY-LI is released from the canine gracilis muscle upon sympathetic nerve stimulation at high frequencies. There is nerve stimulation evoked vasoconstriction, which is resistant to alpha-adrenoceptor blockade. This may in part be mediated by NPY released together with NA from the sympathetic vascular nerves.     

Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of beta-adrenoceptors.

The present experiments were undertaken to study the balance between vascular alpha- and beta-adrenoceptors in canine subcutaneous adipose tissue during sympathetic nerve stimulation and noradrenaline injections. Propranolol potentiated and prolonged the vasoconstrictor response to close i.a. injections of noradrenaline. The vasoconstriction induced by brief nerve stimulation (0.5 to 8 Hz) was, however, unaltered by the beta-adrenoceptor blockade. During prolonged nerve stimulation the vasoconstrictor response was well maintained at 1.5 Hz but at 4 Hz there was a gradual escape. The escape phenomenon at 4 Hz was diminished by propranolol. The beta1-selective antagonist practolol, like propranolol, potentiated and prolonged the vasoconstriction induced by noradrenaline injections and reduced the vasoconstrictor escape during prolonged nerve stimulation at 4 Hz. Furthermore, the vasodilatation induced by noradrenaline injection or nerve stimulation during alpha-adrenoceptor blockade was diminished by practolol. Practolol also blocked the lipolytic response to noradrenaline and nerve stimulation. The beta2-selective antagonist H35/25 blocked the effects of the beta2-selective agonist salbutamol but failed to alter noradrenaline as well as nerve stimulation induced vascular and lipolytic beta-adrenoceptor responses. The present results provide further support for the hypothesis that vascular beta-adrenoceptors in adipose tissue are humoral (noninnervated), preferentially activated by circulating noradrenaline. Moreover, both vascular and lipolytic beta-adrenoceptors activated by noradrenaline in adipose tissue are best classified as beta1-adrenoceptors.     

Metabolic effects of blood flow restriction in adipose tissue.

The metabolic effects of blood flow restriction were studied in isolated blood-perfused canine subcutaneous adipose tissue. Blood flow restriction (on the average to 20 per cent of control flow) was caused by either mechanical clamping of the arterial inflow or by i.a. injections of methoxamine or angiotensin. Glucose uptake in the adipose tissue was reduced during blood flow restriction. This was partially compensated for by a period of increased glucose uptake following restoration of flow. Blood flow restriction also caused an increase in the venous lactate/pyruvate ratio. The basal lipolytic rate was decreased during blood flow restriction. Lipolysis induced by brief (5 min) sympathetic nerve stimulation (4 Hz) was not inhibited by blood flow restriction as the total amount of glycerol released from the tissue was unaffected. The outflow rate was reduced during blood flow restriction, but glycerol trapped within the tissue was apparently not reutilized by the fat cells as it was released upon flow restroation. FFA outflow following nerve stimulation was, however, inhibited suggesting increased reutilization of FFA within the tissue. This increased reutilization may ultimately be caused by the observed change in red./ox.-balance and/or by the limited carrier capacity (albumin) available during blood flow restriction. Three main conclusions may be drawn from the present results. Firstly, plasma levels of glycerol and FFA do not necessarily reflect adipose tissue lipolysis at a given moment. Secondly, the decreased adipose tissue blood flow seems to be a major cause of the lowered FFA-levels during hemorrhage. Thirdly, in contrast to hemorrhage, even severe reduction of adipose tissue blood flow is insufficient to cause irreversible ischemic damage.     

Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of β-adrenoceptors

The present experiments were undertaken to study the balance between vascular α- and β-adrenoceptors in canine subcutaneous adipose tissue during sympathetic nerve stimulation and noradrenaline injections. Propranolol potentiated and prolonged the vasoconstrictor response to close i.a. injections of noradrenaline. The vasoconstriction induced by brief nerve stimulation (0.5 to 8 Hz) was, however, unaltered by the β-adrenoceptor blockade. During prolonged nerve stimulation the vasoconstrictor response was well maintained at 1.5 Hz but at 4 Hz there was a gradual escape. The escape phenomenon at 4 Hz was diminished by propranolol. The β₁-selective antagonist practolol, like propranolol, potentiated and prolonged the vasoconstriction induced by noradrenaline injections and reduced the vasoconstrictor escape during prolonged nerve stimulation at 4 Hz. Furthermore, the vasodilatation induced by noradrenaline injection or nerve stimulation during α-adrenoceptor blockade was diminished by practolol. Practolol also blocked the lipolytic response to noradrenaiine and nerve stimulation. The β₂-selective antagonist H35/25 blocked the effects of the β₂-selective agonist salbutamol but failed to alter noradrenaline as well as nerve stimulation induced vascular and lipolytic β-adrenoceptor responses. The present results provide further support for the hypothesis that vascular β-adrenoceptors in adipose tissue are humoral (noninnervated), preferentially activated by circulating noradrenaline. Moreover, both vascular and lipolytic β-adrenoceptors activated by noradrenaline in adipose tissue are best classified as β₁-adrenoceptors.     

Effect of Sympathetic Nerve Stimulation on Net Transvascular Movement of Fluid in Canine Adipose Tissue

Net transvascular movement of fluid has been studied in the isolated, autoperfused subcutaneous adipose tissue of the dog, during and after sympathetic nerve stimulation (1–15 Hz) and during infusion of 50% glucose i.a. Net fluid movement was calculated as the difference between change in tissue volume and change in blood volume. Tissue volume was measured by plethysmography and blood volume by external monitoring of circulating ¹³¹I-albumin. No net fluid movement of statistical significance was found during or after nerve stimulation except during the first minute of stimulation at 15 Hz when a small net absorption (p<0.05) was obtained. In contrast, infusion of glucose at 25–75 mOsm/kg H₂O produced a dose-dependent net absorption lasting several minutes, amounting maximally to 0.30 ml × min^-1× 100 g^-1. The absence of prolonged net absorption in subcutaneous adipose tissue during nerve stimulation as well as the absence of net filtration after stimulation may be explained by an essentially unaltered mean hydrostatic capillary pressure. The results indicate that adipose tissue does not contribute to the fluid homeostasis of the body via sympathetic resetting of the pre-postcapillary resistance ratio. Thus, mobilisation of fluid from the nterstitial space in adipose tissue into the blood does not seem to occur by nerve activity.     

Evidence that transmitter can be released from regions of the nerve cell other than presynaptic axon terminal: axonal release of acetylcholine without modulation

Release of acetylcholine from isolated preganglionic axons of sympathetic nerve trunk (cervical preganglionic sympathetic branch) of the cat was studied. In response to depolarization (KCl, 48.4 mM) acetylcholine was released into the eserinized Krebs solution. This release was shown to be dependent on extracellular Ca2+. Electrical stimulation (1 Hz) enhanced the release of acetylcholine from the isolated axonal preparation. The release by stimulation proved to be tetrodotoxin-sensitive and Ca2+-dependent. Evidence has been obtained that the acetylcholine released from sympathetic nerve trunks originates from the axon and not from Schwann cells: 5 days after section of the nerve, there was no release in response to stimulation. The release of acetylcholine from the axon is unlike that from axon terminals in that the rate of release cannot be enhanced by the inhibition of Na, K-adenosine 5'-triphosphatase (ouabain 2 X 10(-5) M) and cannot be modulated by noradrenaline (10(-6) M) or by morphine. Furthermore, although isolated nerve trunks took up [3H]choline by a hemicholinium-sensitive process, no radioactivity could be released upon electrical stimulation. It is suggested that the release of acetylcholine is not confined to axon terminals, but that it can be non-synaptically released by depolarization from axons provided Ca2+ is present.     

Evaluation of presynaptic alpha-receptor function in the canine renal vascular bed

The functional significance of presynaptic alpha-receptor modulation of sympathetic nerves was examined in vivo in the canine renal vascular bed. In pentobarbital-anesthetized dogs, the vasoconstrictor response to renal nerve stimulation and exogenous norepinephrine was compared before and during intra-arterial infusions of epinephrine, oxymetazoline, clonidine, and norepinephrine. Only epinephrine produced a modest decrease in stimulation-induced vasoconstriction at 1 Hz. After pretreatment with desipramine, intra-arterial infusions of epinephrine or norepinephrine did not alter stimulation-induced vasoconstrictor responses relative to exogenous norepinephrine. Further, neither yohimbine nor phentolamine (10(-9) to 10(-3) g, intra-arterial) produced a distinctly increased vasoconstrictor response to nerve stimulation relative to exogenous norepinephrine. Thus, studies using alpha-receptor agonists, antagonists, and inhibition of neuronal uptake failed to reveal a physiologically significant alpha-receptor-mediated negative feedback mechanism for stimulation-induced vasoconstriction in the canine renal vascular bed.     

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 GMP 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 < 0.01), while the cyclic AMP content increased by 50 % (p < 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 a-receptor blockade. It is concluded that 1) sympathetic nerve stimulation 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.     

The Effect of Lactate in Canine Subcutaneous Adipose Tissue in Situ1

Fredholm , B. B. The effect of lactate in canine subcutaneous adipose tissue in situ. Acta physiol. scand. 1971. 81. 110–123. Na-L(+)-lactate and Na-pyruvate were administered by intraarterial infusion in canine subcutaneous adipose tissue, perfused with the dogs own blood either at a constant rate from a reservoir or by autoperfusion. The glucose uptake was found to be dependent upon the arterial glucose concentration. Similarly the uptake of lactate and pyruvate increased with increasing arterial concentrations, the latter more rapidly than the former. Infusion of Na-L(+)-lactate below 5 mM and Na-D(—)-lactate (10–11 mM) had no effect on the release of FFA and glycerol upon nerve stimulation (4 cps for 5 to 10 min). On the other hand Na-L(+)-lactate above 10 mM caused a 70 per cent inhibition of the release of FFA without significantly affecting the glycerol release. Na-pyruvate (5 mM) decreased the glycerol output significantly, but increased the FFA release. Neither of the anions had any significant effect on the glucose uptake. Na-lactate was not vasoactive, whereas Na-pyruvate was slightly vasodilator. It is concluded that lactate in concentrations occurring a.g. during muscular exercise and shock is capable of significantly depressing the rate of FFA release upon nerve stimulation by increasing the rate of re-esterification. The finding that lactate and pyruvate had opposite effects on esterification indicates a role of the cytoplasmatic NADH/NAD ratio in determining the rate of esterification.     

Metabolic effects of blood flow restriction in adipose tissue

The metabolic effects of blood flow restriction were studied in isolated blood-perfused canine subcutaneous adipose tissue. Blood flow restriction (on the average to 20 per cent of control flow) was caused by either mechanical clamping of the arterial inflow or by i.a. injections of methoxamine or angiotensin. Glucose uptake in the adipose tissue was reduced during blood flow restriction. This was partially compensated for by a period of increased glucose uptake following restoration of flow. Blood flow restriction also caused an increase in the venous lactate/pyruvate ratio. The basal lipolytic rate was decreased during blood flow restriction. Lipolysis induced by brief (5 min) sympathetic nerve stimulation (4 Hz) was not inhibited by blood flow restriction as the total amount of glycerol released from the tissue was unaffected. The outflow rate was reduced during blood flow restriction, but glycerol trapped within the tissue was apparently not reutilized by the fat cells as it was released upon flow restoration. FFA outflow following nerve stimulation was, however, inhibited suggesting increased reutilization of FFA within the tissue. This increased reutiliza-tion may ultimately be caused by the observed change in red./ox.-balance and/or by the limited carrier capacity (albumin) available during blood flow restriction. Three main conclusions may be drawn from the present results. Firstly, plasma levels of glycerol and FFA do not necessarily reflect adipose tissue lipolysis at a given moment. Secondly, the decreased adipose tissue blood flow seems to be a major cause of the lowered FFA-levels during hemorrhage. Thirdly, in contrast to hemorrhage, even severe reduction of adipose tissue blood flow is insufficient to cause irreversible ischemic damage.     

肺血管内皮细胞对交感神经末梢去甲肾上腺素释放的影响

ｃＧＭＰ升高抑制肾上腺能神经末梢释放去甲肾上腺素（ＮＥ），内皮细胞释放的舒张因子（ＥＤＲＦ）增加ｃＧＭＰ，故其对交感神经ＮＥ的释放可能有调节作用。本文观察去内皮细胞或抑制ＥＤＲＦ合成后肺血管对跨膜交感神经刺激（ＴＮＳ）的反应及对２－〔１４Ｃ〕－ＮＥ的摄取和释放。利用磨擦损伤内皮细胞后或使用ＬＮＭＭＡ抑制ＥＤＲＦ合成后，肺血管对ＴＮＳ刺激的反应明显增加，尤以低频率刺激为甚。肺血管对２－〔１４Ｃ〕－Ｎ     

Participation of the parasympathetic and sympathetic nerves in regulation of gallbladder motility in the dog

The participation of the parasympathetic and sympathetic nerves in the canine gallbladder motility was examined. Efferent stimulation of the parasympathetic (vagus) and sympathetic (celiac) nerves caused contraction or inhibition of the neck, body and fundus of the gallbladder. The contractile response induced by vagus nerve stimulation was reduced by subthreshold efferent stimulation of the celiac nerve, while the inhibitory response was neither reduced nor enhanced by subthreshold efferent stimulation of the celiac nerve. The contractile and inhibitory response induced by celiac nerve stimulation was not reduced in the neck, body and fundus by subthreshold efferent stimulation of the vagus nerve. The contractile response to vagus nerve stimulation was reversed to a relaxant response by atropine administration, which was reduced or abolished by hexamethonium. It is suggested that the vagus nerve-induced contractile response in the canine gallbladder is modulated by sympathetic nerves presynaptically at the vagus nerve endings in the enteric ganglion, but the vagus nerve-induced relaxant response, which probably was induced by non-adrenergic non-cholinergic inhibitory neurons, is not modulated by the sympathetic nerves.     

Inhibition of the Lipolytic Response to Nerve Stimulation during Acidosis

Acidosis inhibits catecholamine-induced lipolysis in vivo and in vitro. The lipolytic response of canine subcutaneous adipose tissue to short (5 min) nerve stimulations at 4 Hz was, however, not influenced by hypercapnic acidosis (pH 7.0). The steady state outflow of glycerol during a prolonged nerve stimulation at 4 Hz was inhibited by 40 per cent (p<0.05) at pH 7.0. Similarly, glycerol outflow during vasodilatation induced by a 4 Hz stimulation in α-blocked adipose tissue was inhibited by 37 per cent (p<0.05). Post-stimulatory glycerol outflow was, however, not influenced by acidosis. This poststimulatory glycerol outflow, which may represent a complex wash-out phenomenon, forms the largest part of the response to short nerve stimulations. It is suggested that steady state, rather than poststimulatory lipolysis should be studied in order to see the influence of treatments such as acidosis on responses to nerve stimulation.