Metabolic and vascular effects of circulating endothelin-1 during moderately heavy prolonged exercise

1995 ◽  
Vol 78 (6) ◽  
pp. 2294-2300 ◽  
Author(s):  
G. Ahlborg ◽  
E. Weitzberg ◽  
J. Lundberg

The aims were to investigate 1) the effects of endothelin-1 (ET-1) during exercise and 2) the influence of exercise on arterial ET-1 levels. Six healthy subjects performed two exercises of 2 h duration at 50% of peak oxygen uptake preceded by intravenous infusion of physiological saline or ET-1 (4 pmol.kg-1.min-1). Blood specimens were taken from arterial and hepatic vein catheters. Arterial ET-1 rose 15-fold during the infusion. Splanchnic blood flow fell after ET-1 and remained lower than in control subjects during exercise (P < 0.001). Splanchnic glucose production was approximately 25% lower compared with control values during the whole exercise period (P < 0.01). Neither heart rate, arterial glucagon, insulin, catecholamines, renin, glucose, lactate, nor glycerol levels differed from control exercise values. The calculated gluconeogenesis from glycerol and lactate did not differ from the control values. ET-1 levels rose approximately twofold in the control exercise (P < 0.01) and in another group of seven subjects performing 1 h of exercise at 70% of peak oxygen uptake (P < 0.001). In conclusion, ET-1 levels increased during exercise without ET-1 administration. In addition, circulating ET-1 has a (direct or indirect) regulatory action on splanchnic blood flow and glucose metabolism during exercise (and possibly under pathophysiological conditions) in humans.

1995 ◽  
Vol 79 (1) ◽  
pp. 141-145 ◽  
Author(s):  
G. Ahlborg ◽  
E. Weitzberg ◽  
J. M. Lundberg

The effect of minimal changes in circulating plasma endothelin-1 (ET-1) was studied in 12 healthy subjects receiving either 60 min of ET-1 (0.2 pmol.kg-1.min-1) or physiological saline intravenously. Blood was drawn from arterial, renal, and central hepatic vein catheters. Arterial ET-1-like immunoreactivity (ET-1-LI) increased from 4.7 +/- 0.4 (SE) to 8.6 +/- 1.0 pmol/l during ET-1 infusion. After 10 min, plasma ET-1-LI had increased to 6.12 +/- 0.29 pmol/l. For comparison the plasma ET-1-LI level was 12.9 +/- 4.2 pmol/in five patients with sepsis syndrome. Mean arterial blood pressure rose from 92 +/- 3 to 99 +/- 4 mmHg. Estimated splanchnic and renal blood flows fell by 18 +/- 5 and 10 +/- 3%, respectively, and splanchnic glucose production fell by 42 +/- 6% within 10 min of the ET-1 infusion and differed compared with corresponding control values. Only estimated splanchnic blood flow had increased 60 min after the ET-1 infusion. No change in splanchnic uptake of lactate or glycerol was seen. In conclusion, we suggest that circulating ET-1 with small or no demonstrable change in plasma concentration interferes with vasoactivity and splanchnic glycogenolyses in health and possibly pathophysiological conditions.


2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.


2000 ◽  
Vol 88 (2) ◽  
pp. 738-744 ◽  
Author(s):  
Ricardo G. Fritzsche ◽  
Edward F. Coyle

This study determined whether cutaneous blood flow during exercise is different in endurance-trained (Tr) compared with untrained (Untr) subjects. Ten Tr and ten Untr men (62.4 ± 1.7 and 44.2 ± 1.8 ml ⋅ kg− 1 ⋅ min− 1, respectively; P < 0.05) underwent three 20-min cycling-exercise bouts at 50, 70, and 90% peak oxygen uptake in this order, with 30 min rest in between. The environmental conditions were neutral (∼23–24°C, 50% relative humidity, front and back fans at 2.5 m/s). Because of technical difficulties, only seven Tr and seven Untr subjects completed all forearm blood flow and laser-Doppler cutaneous blood flow (CBF) measurements. Albeit similar at rest, at the end of all three exercise bouts, forearm blood flow was ∼40% higher in Tr compared with Untr subjects (50%: 4.64 ± 0.50 vs. 3.17 ± 0.20, 70%: 6.17 ± 0.61 vs. 4.41 ± 0.37, 90%: 6.77 ± 0.62 vs. 5.01 ± 0.37 ml ⋅ 100 ml− 1 ⋅ min− 1, respectively; n = 7; all P < 0.05). CBF was also higher in Tr compared with Untr subjects at all relative intensities ( n = 7; all P < 0.05). However, esophageal temperature was not different in Tr compared with Untr subjects at the end of any of the aforementioned exercise bouts (50%: 37.8 ± 0.1 vs. 37.9 ± 0.1°C, 70%: 38.1 ± 0.1 vs. 38.1 ± 0.1°C, and 90%: 38.8 ± 0.1 vs. 38.6 ± 0.1°C, respectively). We conclude that a higher CBF may allow Tr subjects to achieve an esophageal temperature similar to that of Untr, despite their higher metabolic rates and thus higher heat production rates, during exercise at 50–90% peak oxygen uptake.


1997 ◽  
Vol 273 (2) ◽  
pp. E348-E354 ◽  
Author(s):  
A. R. Coggan ◽  
C. A. Raguso ◽  
A. Gastaldelli ◽  
B. D. Williams ◽  
R. R. Wolfe

To determine whether alterations in insulin and/or glucagon secretion play an important role in stimulating glucose production (Ra) during intense but submaximal exercise, we studied six untrained subjects during 30 min of cycling at 80% of peak oxygen uptake on two occasions: once under control conditions and once when alterations in insulin and glucagon secretion were prevented with the use of the pancreatic islet clamp technique. In the latter experiments, glucose was infused during exercise to match glycemia with control levels. Glucose kinetics were measured in both trials using a primed, continuous infusion of [6,6-2H]glucose. In the control trial, glucose Ra rose from 11.9 +/- 0.8 mumol.min-1.kg-1 at rest to 42.5 +/- 4.3 mumol.min-1.kg-1 by the end of exercise. A similar increment was observed in the islet clamp experiments, with endogenous Ra peaking at 37.2 +/- 7.9 mumol.min-1.kg-1. This was true even through glucagon concentration did not change from basal and insulin concentration actually rose (the latter apparently due to a decrease in insulin clearance during intense exercise). Thus neither decrements in insulin or increments in glucagon are apparently required to stimulate glucose Ra under the present conditions. Because epinephrine levels rose only slightly, it appears that either neurally released norepinephrine or some other, as yet unidentified, factor is responsible for stimulating glucose Ra during intense but submaximal exercise.


1996 ◽  
Vol 271 (3) ◽  
pp. E496-E504 ◽  
Author(s):  
T. Brundin ◽  
R. Branstrom ◽  
J. Wahren

The metabolic and circulatory responses to intravenous or oral administration of glucose (75 g) were studied in healthy subjects. Pulmonary oxygen uptake increased promptly after oral but not during intravenous glucose infusion. The average 2-h rise above basal in whole body oxygen uptake was 8 +/- 1% (P < 0.001) after oral glucose and 3 +/- 1% (P < 0.05) during intravenous glucose infusion. After oral glucose, splanchnic oxygen uptake rose initially by approximately 15% (P < 0.01) and then declined; its average 2-h postprandial level was not significantly higher than that in the basal state. During intravenous glucose, splanchnic oxygen uptake decreased gradually during the first 75 min, reaching a level approximately 25% below basal (P < 0.05). Oxygen consumption by extrasplanchnic tissues rose significantly and to a similar extent (8%, 2 h average) with both intravenous and oral glucose. Splanchnic blood flow increased significantly after oral but not during intravenous glucose. It is concluded that 1) intravenous infusion and oral glucose administration elicit extrasplanchnic thermogenic effects of similar magnitude, 2) during intravenous glucose infusion, the extrasplanchnic thermogenic effect is counterbalanced by a simultaneous reduction in splanchnic oxygen uptake, resulting in a minimal (3%) net rise in whole body oxygen uptake, and 3) oral glucose ingestion but not intravenous glucose infusion increases the splanchnic blood flow.


1997 ◽  
Vol 272 (4) ◽  
pp. E678-E687 ◽  
Author(s):  
T. Brundin ◽  
A. K. Aksnes ◽  
J. Wahren

The aim of the study was to assess the possible contribution of adrenergic mechanisms to the thermogenic and circulatory effects of glucose ingestion. With the use of indirect calorimetry and arterial, pulmonary arterial, and hepatic venous catheterization, whole body and splanchnic oxygen uptake and blood flow were examined in nine propranolol-treated healthy male volunteers before and during 2 h after oral ingestion of 75 g of glucose. The glucose effects were compared with those in nine untreated controls. After propranolol, the glucose-induced rise in splanchnic blood flow was reduced by approximately 60%, and the hepatic venous glucose release to the systemic circulation was significantly delayed. Glucose-induced increments in pulmonary and splanchnic oxygen uptake and cardiac output were similar in the two groups. It is concluded that adrenergic mechanisms contribute to the glucose-induced rise in splanchnic blood flow and thereby probably to the time course for intestinal absorption of nutrients. It is suggested that the magnitude of glucose-induced thermogenesis is independent of adrenergic stimulation.


1999 ◽  
Vol 87 (1) ◽  
pp. 111-115 ◽  
Author(s):  
R. Bergeron ◽  
M. Kjaer ◽  
L. Simonsen ◽  
J. Bülow ◽  
H. Galbo

The present study compared the arteriohepatic venous (a-hv) balance technique and the tracer-dilution method for estimation of hepatic glucose production during both moderate and heavy exercise in humans. Eight healthy young men (aged 25 yr; range, 23–30 yr) performed semisupine cycling for 40 min at 50.4 ± 1.5(SE)% maximal O2 consumption, followed by 30 min at 69.0 ± 2.2% maximal O2 consumption. The splanchnic blood flow was estimated by continuous infusion of indocyanine green, and net splanchnic glucose output was calculated as the product of splanchnic blood flow and a-hv blood glucose concentration differences. Glucose appearance rate was determined by a primed, continuous infusion of [3-3H]glucose and was calculated by using formulas for a modified single compartment in non-steady state. Glucose production was similar whether determined by the a-hv balance technique or by the tracer-dilution method, both at rest and during moderate and intense exercise ( P > 0.05). It is concluded that, during exercise in humans, determination of hepatic glucose production can be performed equally well with the two techniques.


1997 ◽  
Vol 23 (1) ◽  
pp. 31-37 ◽  
Author(s):  
A. Meier-Hellmann ◽  
D. L. Bredle ◽  
M. Specht ◽  
C. Spies ◽  
L. Hannemann ◽  
...  

1993 ◽  
Vol 264 (4) ◽  
pp. E504-E513 ◽  
Author(s):  
T. Brundin ◽  
J. Wahren

The contribution of the splanchnic tissues to the initial 2-h rise in whole body energy expenditure after ingestion of glucose or fructose was examined in healthy subjects. Indirect calorimetry and catheter techniques were employed to determine pulmonary gas exchange, cardiac output, splanchnic blood flow, splanchnic oxygen uptake, and blood temperatures before and for 2 h after ingestion of 75 g of either fructose or glucose in water solution or of water only. Fructose ingestion was found to increase total oxygen uptake by an average of 9.5% above basal levels; the corresponding increase for glucose was 8.8% and for water only 2.5%. The respiratory exchange ratio increased from 0.84 in the basal state to 0.97 at 45 min after fructose ingestion and rose gradually after glucose to 0.86 after 120 min. The average 2-h thermic effect, expressed as percent of ingested energy, was 5.0% for fructose and 3.7% for glucose (not significant). Splanchnic oxygen consumption did not increase measurably after ingestion of either fructose or glucose. The arterial concentration of lactate rose, arterial pH fell, and PCO2 remained essentially unchanged after fructose ingestion. Glucose, but not fructose, elicited increases in cardiac output (28%) and splanchnic blood flow (56%). Fructose, but not glucose, increased arterial blood temperature significantly. It is concluded that both fructose and glucose-induced thermogenesis occurs exclusively in extrasplanchnic tissues. Compared with glucose, fructose ingestion is accompanied by a more marked rise in CO2 production, possibly reflecting an increased extrasplanchnic oxidation of lactate and an accumulation of heat in the body.


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