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     

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.     

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.     

Release of adenosine-like material from isolated perfused dog adipose tissue following sympathetic nerve stimulation and its inhibition by adrenergic alpha-receptor blockade.

Following the intraarterial infusion of 3H-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 alpha-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 alpha-receptor stimulation. Since adenosine is a potent inhibitor of catecholamine induced lipolysis in this tissue the possibility of a regulatory role must be considered.     

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.     

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.     

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.     

Effect of adenosine, adenosine analogues and drugs inhibiting adenosine inactivation on lipolysis in rat fat cells

It has been suggested that adenosine may be a physiologically important modulator of lipolysis. In the present study it was found that adenosine inhibited lipolysis stimulated by low (0.03 micrometer) concentrations of noradrenaline (NA). Lipolysis stimulated by higher concentrations (0.3 and 3 micrometer) of NA was inhibited to a minor degree or not at all. Theophylline (1 micromete)-induced lipolysis was inhibited by adenosine (IC50 approximately 10 micrometer). Inhibition of theophylline-induced lipolysis was tested for several analogues of adenosine. Some N6-substituted adenosine analogues and 2-Cl-adenosine were more potent inhibitors. Adenine-nucleotides (ATP, ADP, AMP) were about equipotent with adenosine. Several adenosine analogues, including its breakdown products were considerably less potent or ineffective. None of the analogues tested inhibited the action of adenosine. Dipyridamol, dilazep and papaverine, which inhibit the uptake of adenosine into cells, caused only a slight enhancement of the antilipolytic effect of adenosine. None of the analogues inhibited the effect of adenosine. It is concluded that adenosine can inhibit lipolysis due to low, "physiological" concentrations of noradrenaline and of low concentration of theophylline via an action on a receptor structure on the cell surface which exhibits structural specificity.     

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.     

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.     

Regulation of thymocyte proliferation by endogenous adenosine and adenosine deaminase

Spontaneous proliferation of thymocytes after 20-25 h of culture was significantly increased by the presence of adenosine deaminase (ADA) or theophylline. The effect of ADA was counteracted by the ADA inhibitor EHNA. When given alone, EHNA inhibited proliferation. This effect was not blocked by inhibition of adenosine uptake with dipyridamol. These results suggest that proliferation in culture is regulated by a balance between endogenous adenosine and ADA, controlling the influence of adenosine on the intracellular cyclic AMP level via an adenosine receptor on the surface of thymocytes. According to the hypothesis, ADA would stimulate proliferation by decreasing extracellular adenosine levels and theophylline by blocking adenosine receptors on thymocytes. EHNA would inhibit proliferation by increasing extracellular adenosine levels. In accordance with this interpretation, the adenosine analogue phenylisopropyl adenosine (PIA) inhibited proliferation and the effect could be inhibited by theophylline. The postulated effect of endogenous adenosine could not be mimicked by a single administration of exogenous adenosine. Whereas most doses of adenosine were without effect, a high dose of adenosine (0.1 mM) in combination with EHNA unexpectedly stimulated proliferation. Since the effect was blocked by dipyridamol, an intracellular site of action for adenosine is suggested in this case.     

Regional variation of white adipocyte lipolysis during the annual cycle of the alpine marmot.

During winter, hibernating animals rely on their lipid stores for survival. In vitro lipolytic activity of isolated adipocytes from gonadal and subcutaneous white adipose tissue (WAT) was studied in captive alpine marmots (Marmota marmota) at two different times of their yearly cycle. During the summer, when marmots were eating, adipocyte responsiveness and sensitivity to isoprenaline and noradrenaline were higher in gonadal than in subcutaneous WAT. During hibernation, when marmots were spontaneously fasting. both the response and sensitivity to catecholamines decreased in gonadal WAT to the level of subcutaneous WAT. A similar pattern of response was also observed when lipolysis was stimulated with glucagon but the lipolytic rate was three times lower than with catecholamines. Adenosine deaminase (ADA) had a marked stimulatory effect on lipolysis, especially during the 'feeding' period, suggesting that adenosine may be a potent lipolytic modulator in marmot adipocytes. It is concluded that in marmots, lipolysis could be differentially regulated between fat depots during the annual cycle possibly to optimize either the building-up or the use of fat reserves.     

Different metabolic regulation by adenosine in omental and subcutaneous adipose tissue

Adenosine content was higher in omental adipose tissue (0.91 +/- 0.13 nmol g-1 of wet weight; mean +/- S.E.M.) than in abdominal subcutaneous adipose tissue (0.42 +/- 0.08 nmol g-1 of wet weight) in rapidly frozen surgical biopsy samples taken from ten patients undergoing elective abdominal surgery. This difference was statistically significant (P less than 0.002). The sensitivity of isoprenaline-stimulated lipolysis to inhibition by N6-(phenylisopropyl)adenosine was studied in omental and abdominal subcutaneous adipocytes isolated from nine patients. The effect of this adenosine Ri-site agonist was less pronounced in omental than in abdominal subcutaneous adipocytes which could be due to a desensitization phenomenon. This difference was statistically significant (P = 0.012). The ratio of the inhibitory guanine nucleotide binding proteins Gi1 and Gi2 to the corresponding stimulatory protein Gs was the same in plasma membranes prepared from omental and abdominal subcutaneous adipocytes. In conclusion, in omental adipose tissue, adenosine content is higher and the response to this nucleoside is less pronounced than in subcutaneous adipocytes. This difference cannot be explained by a different (Gi1 + Gi2)/Gs ratio.     

Effects of dipyridamole and theophylline on reactive hyperaemia in subcutaneous adipose tissue in humans

The importance of adenosine for reactive hyperaemia in subcutaneous adipose tissue was studied in healthy volunteers, using the adenosine uptake inhibitor dipyridamole (bolus 0.1 mg/kg i.v. followed by infusion of 0.7 microgram/kg/min) and the adenosine receptor antagonist theophylline (4 or 6 mg/kg i.v.). Basal blood flow, total blood flow and hyperaemia (total minus basal flow) after a 20-min arterial occlusion were measured in the distal femoral region by the 133Xe washout technique with and without drug treatment. Basal blood flow (mean +/- SEM) was 2.4 +/- 0.3 ml/min/100 g, while total post-occlusive flow and total reactive hyperaemia were 97.3 +/- 8.4 and 61.8 +/- 6.5 ml/100 g, respectively, without drug treatment. Basal blood flow was unaffected by dipyridamole but the total flow and hyperaemia were enhanced by 49 +/- 24 and 60 +/- 31%, respectively (P less than 0.05 for both). This enhancement was due to increases in both amplitude and duration of the hyperaemia. Neither basal blood flow, total post-occlusive flow nor hyperaemia were significantly altered by theophylline. The amplitude of the enhanced hyperaemia during dipyridamole was not significantly counteracted by simultaneous theophylline treatment (6 mg/kg) but the duration of hyperaemia was reduced from 13 +/- 1 to 8 +/- 1 min (P less than 0.01). The results suggest that endogenous adenosine does not regulate basal blood flow or reactive hyperaemia of limited duration in human adipose tissue. However, reactive hyperaemia may be enhanced by pharmacological elevation of endogenous adenosine levels.     

The disappearance of adenosine from blood and platelet suspension in relation to the platelet cyclic AMP content

Adenosine exerts anti-aggregatory effects on human platelets in vitro, probably by increasing intraplatelet levels of cyclic AMP. In addition, adenosine prevents platelet loss in vivo. We have studied the relationship between the concentration of adenosine in the platelet media and the level of cAMP. In PRP, exogenous adenosine (2-16 microM) was eliminated with a half-life close to 5 min. Approximately half of the added adenosine was deaminated (blocked by 1-2 microM EHNA), and half was eliminated by uptake into platelets (blocked by 2 microM dipyridamole). In whole blood the half-life for adenosine was much shorter, about 15 s. Addition of adenosine deaminase (0.3 microgram ml-1) to PRP resulted in a measured half-life for adenosine approximating that of whole blood. In PRP where adenosine was eliminated as quickly as in whole blood, the adenosine-mediated stimulation of cAMP was 35% lower than in PRP, and the cAMP response lasted 2 min versus 15 min in normal PRP. These results suggest that the magnitude and duration of adenosine's effect on platelets are markedly overestimated by studying platelet suspensions. In blood, the effect of adenosine is smaller in magnitude and very transient. The possibility is discussed that the action of adenosine in vivo on blood platelets can therefore be quite local.     

Direct Antilipolytic Effect of Acidosis in Isolated Rat Adipocytes

The possibility that acidosis inhibits lipolysis indirectly by causing ionic shifts or by favouring the accumulation of an inhibitor has been tested in isolated fat cells. Lipolysis induced by 3 μM noradrenaline (NA) was inhibited by 40–60% and that induced by 1 mM theophylline (THEO) by about 75% when the pH was reduced to 6.6. Lipolysis induced by NA+THEO was inhibited by 20–30%. Changing the concentration of Ca⁺⁺or Mg⁺⁺did not alter the degree of inhibition. Reducing the K⁺-ion concentration enhanced the inhibitory effect of low pH on lipolysis induced by NA or NA + THEO, whereas cyclic AMP accumulation was uninfluenced. Omitting glucose from the incubation medium caused a slight enhancement of pH-induced inhibition of lipolysis (from 60 to 70%, p<0.01). Reducing the concentration of albumin, which binds inhibitory substances such as FFA, reduced lipolysis more at normal than at reduced pH. At high FFA/albumin ratios (5 or above) lipolysis was similar at normal and reduced pH. The antilipolytic effect of decreased pH was equally pronounced in perifused fat cells, where inhibitory substances are not allowed to accumulate. Our results suggest that the antilipolytic effect of acidosis is mainly a direct effect of the increase in H⁺ion concentration. The inhibitory effect of acidosis on various responses to β-adrenoceptor stimulation may be caused by a decreased formation of cyclic AMP in turn caused directly by the decrease in pH.     

Cyclic AMP-dependent and independent inhibition of lipolysis by adenosine and decreased pH.

NA-stimulated lipolysis and cAMP formation in isolated rat fat cells is inhibited by acidosis. In the present report we have examined the quantitative relationship between lipolysis and cAMP formation at normal and reduced pH and the possible involvement of adenosine, an endogenous inhibitor of cAMP formation. Adenosine antagonized cAMP accumulation and to a considerably lower degree lipolysis, effects potentiated by acidosis. Theophylline, an antagonist of adenosine effects, stimulated lipolysis and cAMP-accumulation, and potentiated responses to NA. Adenosine deaminase (ADA) had theophylline-like effects. Acidosis inhibited lipolysis and cAMP accumulation induced by ADA and theophylline to a larger extent than those induced by NA. It is suggested that adenosine modulates fat cell cAMP production and may contribute to the antilipolytic effect of acidosis. There was a curvilinear relationship between cAMP elevation and glycerol production in fat cell suspensions, which was different at pH 7.4 and at pH 6.6. The amount of cAMP needed for half-maximal activation of lipolysis increased from 1.3 (pH 7.4) to 3.1 pMol X 10(-5) cells (pH 6.6). The maximal glycerol production was reduced from 1 300 to 900 nMol X 10(-5) cells. The antilipolytic effect of acidosis is apparently due partly to an inhibition of cAMP formation and partly to inhibition of subsequent step(s) in the activation sequence.     

Effect of reflex stimuli on vascular resistance and glycerol release in in vivo dog subcutaneous adipose tissue

Summary Although direct autonomic nerve stimulation and infusion of catecholamine has been shown to result in substantial amounts of lipolysis in dog subcutaneous adipose tissue, there is no evidence to indicate that reflex autonomic stimulation will result in qualitatively and quantitatively similar changes. The present studies were, performed to evaluate the effects of reflex autonomic stimulation on vascular resistance and glycerol release in isolated, innervated and blood-perfused subcutaneous fat pad. Autonomic nerve stimulation at physiological frequencies was performed and resulted in release of glycerol that was compatible with previously reported data. Reflex stimulation by moderate and severe hypoxemia did not result in a significant glycerol release, but a maximal reflex stimulus (ventricular fibrillation) did. Since the majority of these reflex stimuli resulted in large changes in vascular resistance, it would appear that reflex hemodynamic changes can occur in these preparations without concommitant changes in glycerol release. Alpha blockade of the vasoconstriction resulted in the appearance of rising glycerol output suggesting that vasoconstriction prevents lipolysis.Supported by: American Heart Association Grant 72-615 and NIH, Medical Cardiology Training Grant HL05635 (Drs. Croke and Longo) and by USPHS Career Developement Award I KOY HF46346 (Dr. Skinner).     

Regional difference in lipolysis caused by a β-adrenergic agonist as determined by the microdialysis technique

We have investigated the difference in lipolysis caused by a β-adrenergic agent between visceral and abdominal subcutaneous adipose tissues in vivo. Glycerol levels (lipolysis index) were continuously monitored in mesenteric and abdominal subcutaneous adipose tissues of anaesthetized Wistar rats using the microdialysis technique. During microdialysis, increasing concentrations of the lipolytic agent, isoproterenol (10^?8, 10^?7, 10^?6, 10^?5 mol L^?1), were added to the perfusion. Glycerol concentrations in dialysate at each isoproterenol concentration, blood glucose concentrations during the experiment, and plasma insulin concentrations before and immediately after the experiment were measured. The effect of isoproterenol on local blood flow was investigated using the ethanol technique. The clearance rate of ethanol from the perfusion medium was used as the index of local blood flow. There was no significant change in blood glucose or plasma insulin concentrations during the study. Glycerol levels in dialysate were significantly higher in mesenteric than in abdominal subcutaneous adipose tissues at all isoproterenol concentrations. The percentage change of baseline ethanol ratio was not altered by increasing isoproterenol concentrations in both mesenteric and subcutaneous adipose tissues. There was also no significant difference in percentage change of the baseline ethanol ratio between mesenteric and abdominal subcutaneous adipose tissues. These results suggest that mesenteric adipose tissue is characterized by an even higher β-adrenergic agonist-induced lipolysis than abdominal subcutaneous adipose tissue.