Lack of effect of [alpha ]- and [beta ]-adrenergic inhibition on forearm glucose uptake despite differences in forearm blood flow in healthy humans

Metabolism ◽  
2002 ◽  
Vol 51 (11) ◽  
pp. 1506-1513 ◽  
Author(s):  
R.P. Hoffman ◽  
C.A. Sinkey ◽  
J.M. Dopp ◽  
B.G. Phillips
2003 ◽  
Vol 55 (6) ◽  
pp. 526-530
Author(s):  
Herbert Langenberger ◽  
Georg Schaller ◽  
Johannes Pleiner ◽  
Friedrich Mittermayer ◽  
Michaela Bayerle-Eder ◽  
...  

1996 ◽  
Vol 271 (3) ◽  
pp. H1182-H1185 ◽  
Author(s):  
M. L. Blitzer ◽  
S. D. Lee ◽  
M. A. Creager

Endothelium-derived nitric oxide (EDNO) contributes to basal systemic vascular resistance under normoxic conditions. The purpose of this investigation was to determine whether EDNO contributes to the regulation of limb vascular resistance during hypoxia in healthy humans. Forearm blood flow was assessed by venous occlusion plethysmography. Hypoxia was induced by delivering a mixture of N2 and O2 via a gas blender adjusted to reduce the PO2 to 50 mmHg. During hypoxia, forearm blood flow increased from 2.4 +/- 0.2 to 3.0 +/- 0.3 ml.100 ml-1.min-1 (P < 0.001), and forearm vascular resistance decreased from 38 +/- 3 to 29 +/- 3 units (P < 0.001). The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 2,000 micrograms/min intra-arterially) was administered to eight subjects. The percent increase in forearm vascular resistance after administration of L-NMMA was greater during hypoxia than normoxia (67 +/- 14 vs. 39 +/- 15%, P < 0.05). L-NMMA reduced the forearm vasodilator response to hypoxia from 27 +/- 3 to 11 +/- 5% (P = 0.01). To exclude the possibility that this attenuated response to hypoxia was a consequence of vasoconstriction and not specific for nitric oxide synthase inhibition, six subjects received intra-arterial phenylephrine. Phenylephrine did not affect the vasodilator response to hypoxia (17 +/- 3 vs. 21 +/- 6%, P = NS). It is concluded that EDNO contributes to hypoxia-induced vasodilation in the forearm resistance vessels in healthy humans.


Metabolism ◽  
1999 ◽  
Vol 48 (12) ◽  
pp. 1575-1583 ◽  
Author(s):  
Robert P. Hoffman ◽  
Christine A. Sinkey ◽  
Eva Tsalikian

2010 ◽  
Vol 47 (2) ◽  
pp. 139-147 ◽  
Author(s):  
M.P. Sonne ◽  
L. H&oslash;jbjerre ◽  
A.C. Alibegovic ◽  
A. Vaag ◽  
B. Stallknecht ◽  
...  

1995 ◽  
Vol 78 (1) ◽  
pp. 172-178 ◽  
Author(s):  
G. A. Ford ◽  
W. D. Dachman ◽  
T. F. Blaschke ◽  
B. B. Hoffman

beta-Adrenergic responses have been shown to decline with aging, particularly in the cardiovascular system. We infused terbutaline, a selective beta 2-adrenoceptor agonist, into the brachial artery of 10 young (mean age 25 yr, range 22–31 yr) and 9 elderly (mean age 73 yr, range 68–81 yr) healthy subjects to examine its effects on nutrient flux. Forearm K+, PO4, free fatty acid (FFA), and glycerol uptake were determined by measurement of forearm blood flow (using dye dilution) and brachial arterial and deep venous plasma substrate concentrations. Elderly subjects were less sensitive to terbutaline-mediated increases in forearm blood flow, net fluxes of K+, and glycerol but not net fluxes of FFA or PO4. The mean fitted slopes of each parameter vs. the log of the terbutaline concentration, a measure of forearm beta-adrenergic sensitivity, for young and elderly groups were 4.9 +/- 1.7 (SD) vs. 2.4 +/- 2.3 for forearm blood flow (P <O 0.05), 0.84 +/- 0.46 vs. 0.43 +/- 0.37 for K+ net flux (P < 0.05), -157 +/- 113 vs. -26 +/- 26 for glycerol net flux (P < 0.01), -336 +/- 429 vs. -44 +/- 457 for FFA net flux (P = 0.11), and 0.31 +/- 0.24 vs. 0.18 +/- 0.16 for PO4 net flux (P = 0.14). Terbutaline promoted net uptake of K+ into skeletal muscle less well in the elderly, although net PO4 flux was similar in the two groups. Terbutaline-stimulated vasodilation and net glycerol efflux but not FFA efflux were impaired with aging. These data demonstrate that heterogeneous changes in beta-adrenergic responses occur with aging.


2002 ◽  
Vol 104 (1) ◽  
pp. 39-46 ◽  
Author(s):  
H.M. Omar FAROUQUE ◽  
Ian T. MEREDITH

Experimental data suggest that vascular ATP-sensitive potassium (KATP) channels may be an important determinant of functional hyperaemia, but the contribution of KATP channels to exercise-induced hyperaemia in humans is unknown. Forearm blood flow was assessed in 39 healthy subjects (23 males/16 females; age 22±4 years) using the technique of venous occlusion plethysmography. Resting forearm blood flow and functional hyperaemic blood flow (FHBF) were measured before and after brachial artery infusion of the KATP channel inhibitors glibenclamide (at two different doses: 15 and 100µg/min) and gliclazide (at 300µg/min). FHBF was induced by 2min of non-ischaemic wrist flexion–extension exercise at 45 cycles/min. Compared with vehicle (isotonic saline), glibenclamide at either 15µg/min or 100µg/min did not significantly alter resting forearm blood flow or peak FHBF. The blood volume repaid at 1 and 5min after exercise was not diminished by glibenclamide. Serum glucose was unchanged after glibenclamide, but plasma insulin rose by 36% (from 7.2±0.8 to 9.8±1.3m-units/l; P = 0.02) and 150% (from 9.1±1.3 to 22.9±3.5m-units/l; P = 0.002) after the 15 and 100µg/min infusions respectively. Gliclazide also did not affect resting forearm blood flow, peak FHBF, or the blood volume repaid at 1 and 5min after exercise, compared with vehicle (isotonic glucose). Gliclazide induced a 12% fall in serum glucose (P = 0.009) and a 38% increase in plasma insulin (P = 0.001). Thus inhibition of vascular KATP channels with glibenclamide or gliclazide does not appear to affect resting forearm blood flow or FHBF in healthy humans. These findings suggest that vascular KATP channels may not play an important role in regulating basal vascular tone or skeletal muscle metabolic vasodilation in the forearm of healthy human subjects.


1989 ◽  
Vol 86 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Frank M. Sacks ◽  
Mark A. Creager ◽  
Shelley J. Gallagher ◽  
Joseph Loscalzo ◽  
Victor J. Dzau

2013 ◽  
Vol 305 (11) ◽  
pp. H1639-H1645 ◽  
Author(s):  
Samson Spilk ◽  
Michael D. Herr ◽  
Lawrence I. Sinoway ◽  
Urs A. Leuenberger

Systemic hypoxia causes skeletal muscle vasodilation, thereby preserving O2 delivery to active tissues. Nitric oxide (NO), adenosine, and prostaglandins contribute to this vasodilation, but other factors may also play a role. We tested the hypothesis that regional inhibition of endothelium-derived hyperpolarizing factor with the cytochrome P-450 2C9 antagonist fluconazole, alone or combined with the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA), attenuates hypoxia-induced vasodilation. We compared forearm blood flow (FBF) and skin blood flow before and during brachial artery infusion of fluconazole (0.3 mg/min; trial 1) or fluconazole + l-NMMA (50 mg over 10 min; trial 2) and during systemic hypoxia (10 min, arterial Po2 ∼37 mmHg) in infused (experimental) and control forearms of 12 healthy humans. During normoxia, fluconazole and fluconazole + l-NMMA reduced ( P < 0.05) forearm vascular conductance (FVC) by ∼10% and ∼18%, respectively. During hypoxia and fluconazole ( trial 1), FVC increased by 1.76 ± 0.37 and 0.95 ± 0.35 units in control and experimental forearms, respectively ( P < 0.05). During hypoxia and fluconazole + l-NMMA ( trial 2), FVC increased by 2.32 ± 0.51 and 0.72 ± 0.22 units in control and experimental forearms, respectively ( P < 0.05). Similarly, during hypoxia with l-NMMA alone ( trial 3; n = 8) FVC increased by 1.51 ± 0.46 and 0.45 ± 0.32 units in control and experimental forearms, respectively ( P < 0.05). These effects were not due to altered skin blood flow. We conclude that endothelium-derived hyperpolarizing factor contributes to basal vascular tone and to hypoxia-induced skeletal muscle vasodilation and could be particularly relevant when other vasodilator systems are impaired.


2002 ◽  
Vol 102 (2) ◽  
pp. 241-246 ◽  
Author(s):  
Lars LIND ◽  
Andreas FUGMANN ◽  
Jonas MILLGÅRD ◽  
Christian BERNE ◽  
Hans LITHELL

In order to evaluate possible differences between men and women with regard to the ability of insulin to induce vasodilatation, promote glucose uptake and enhance endothelium-dependent vasodilatation, 12 young (22-28 years), non-obese women and 15 corresponding males were subjected to 2h of euglycaemic hyperinsulinaemia (insulin infusion rate of 56m-unitsċmin-1ċm-2). Forearm blood flow was measured by venous occlusion plethysmography. Endothelium-dependent vasodilatation was evaluated by the local intra-arterial infusion of methacholine into the brachial artery (2-4μg/min). The cardiac index was measured by thoracic bioimpedance. A 2h period of hyperinsulinaemia increased the plasma insulin concentration to a similar degree in both sexes (females, 84±8.8m-units/l; males, 87±7.5m-units/l), but induced a more marked increase in forearm blood flow in females than in males (+104±67% and +52±30% respectively; P < 0.01; 95% confidence interval for difference 11-94%). Furthermore, a significant decrease in total peripheral resistance (-20±6.9%; P < 0.01) and an increase in cardiac index (+23±13%; P < 0.01) were seen in women only (P < 0.05 compared with men). Blood pressure and heart rate were not altered in either sex. Whole-body insulin-mediated glucose uptake and forearm glucose uptake did not differ between the sexes, and the ability of insulin to enhance endothelium-dependent vasodilatation (+19%; P < 0.01) was similar in men and women. In conclusion, the present study shows that the ability of insulin to cause vasodilatation was greater in non-obese young women compared with men. However, no differences between the sexes were seen with regard to insulin-mediated glucose uptake and the ability of insulin to enhance endothelium-dependent vasodilatation.


1988 ◽  
Vol 255 (6) ◽  
pp. E953-E958 ◽  
Author(s):  
E. Ferrannini ◽  
S. Taddei ◽  
D. Santoro ◽  
A. Natali ◽  
C. Boni ◽  
...  

Insulin promotes potassium uptake into skeletal muscle by stimulating the activity of the Na+-K+ pump. To test whether insulin-induced glucose and potassium uptake are linked processes in vivo, we used the perfused forearm technique in healthy volunteers. Local hyperinsulinemia (125 +/- 11 microU/ml for 100 min) induced a net uptake of glucose and potassium (4.79 +/- 0.61 and 0.76 +/- 0.22 mumol.min-1.100 ml-1 of forearm volume, respectively). When an intra-arterial ouabain infusion (0.72 microgram.min-1.100 ml-1, producing local levels of approximately 0.5 mM) was superimposed on the insulin infusion, potassium uptake was blocked (0.026 +/- 0.190 ml.min-1.100 ml-1, P less than 0.02), and glucose uptake was decreased (to 3.31 +/- 0.34 mumol.min-1.100 ml-1, P less than 0.03). The latter change was explained by a 30% fall in forearm blood flow (from 2.95 +/- 0.10 to 2.01 +/- 0.18 ml.min-1.100 ml-1, P less than 0.001). To separate out the effect of blood flow, in another series of studies forearm blood flow was clamped by co-infusing propranolol and phentolamine (7 and 8 micrograms.min-1.100 ml-1, respectively). Under these conditions of fixed flow (7.0 +/- 0.8 ml.min-1.100 ml-1), ouabain still abolished the stimulatory effect of insulin on potassium uptake but had only a small (and statistically insignificant) effect on forearm glucose extraction (from 20 +/- 2 to 16 +/- 2%, P = N>). We conclude that in human forearm muscle ouabain inhibits Na+-K+ exchange and depresses insulin-induced glucose uptake via an adrenergic-mediated limitation of blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)


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