Acclimatization to high altitude increase muscle sympathetic activity both at rest and during exercise

This investigation examined the relationship between alterations in plasma norepinephrine associated with 21 days of high-altitude exposure and muscle sympathetic activity both at rest and during exercise. Healthy sea level residents, divided into a control group (n = 5) receiving a placebo or a drug group (n = 6) receiving 240 mg/day of propranolol, were studied while at sea level, upon arrival (acute), and after 21 days of residence (chronic) at 4,300 m. Arterial norepinephrine levels and net leg uptake and release of norepinephrine were determine both at rest and during 45 min of submaximal exercise via samples collected from femoral arterial and venous catheters. Arterial norepinephrine levels increased significantly after chronic altitude exposure both at rest (84%) and during exercise (174%) compared with sea level and acute values. A net uptake of norepinephrine was found in resting legs at sea level (0.28 +/- 0.05 nmol/min) and with acute exposure (0.07 +/- 0.06 nmol/min); however, a significant switch to net leg norepinephrine release was observed with chronic altitude exposure (0.51 +/- 0.11 nmol/min). With exercise, a net release of norepinephrine by the leg occurred across all conditions with chronic exposure, again eliciting the greatest values (5.3 +/- 0.6, 8.0 +/- 1.7, and 14.4 +/- 3.1 nmol/min for sea level, acute, and chronic exposure, respectively). It was concluded that muscle sympathetic activity is significantly elevated both at rest and during submaximal exercise as a result of chronic high-altitude exposure, and muscle is a major contributor to the increase in plasma norepinephrine levels associated with prolonged altitude exposure. The presence of dense beta-blockade did not alter this adaptation to altitude.

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Arterial catecholamine responses during exercise with acute and chronic high-altitude exposure

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.261.4.e419 ◽

1991 ◽

Vol 261 (4) ◽

pp. E419-E424 ◽

Cited By ~ 35

Author(s):

R. S. Mazzeo ◽

P. R. Bender ◽

G. A. Brooks ◽

G. E. Butterfield ◽

B. M. Groves ◽

...

Keyword(s):

High Altitude ◽

Sea Level ◽

Neural Activity ◽

Chronic Exposure ◽

Physiological Responses ◽

Submaximal Exercise ◽

Altitude Exposure ◽

Acute And Chronic Exposure ◽

Over Time ◽

Catecholamine Levels

Exercise at high altitude is a stress that activates the sympathoadrenal systems, which could affect responses to acute altitude exposure and promote adaptations during chronic altitude exposure. However, catecholamine levels are not clearly described over time at high altitude. In seven male volunteers (23 yr, 72 kg), resting arterial norepinephrine concentrations (ng/ml) on arrival at Pikes Peak (0.338 +/- 0.041) decreased compared with sea-level values (0.525 +/- 0.034) but increased to above sea-level values after 21 days at 4,300 m (0.798 +/- 0.052). Furthermore, during 45 min of constant submaximal exercise, values were similar at sea level (1.670 +/- 0.221) and on acute exposure to 4,300 m (2.123 +/- 0.086) but increased after 21 days of chronic exposure (2.693 +/- 0.216). By contrast, resting arterial epinephrine values (ng/ml) during acute and chronic exposure (0.708 +/- 0.033 vs. 0.448 +/- 0.026) both exceeded those of sea level (0.356 +/- 0.020). During exercise values on arrival were greater than at sea level (0.921 +/- 0.024 vs. 0.397 +/- 0.035) but fell to 0.612 +/- 0.025 ng/ml after 21 days. Exercise norepinephrine levels were related to systemic vascular resistance measurements (r = 0.93), whereas epinephrine levels were related to circulating lactate (r = 0.95). We conclude that during exercise at altitude there is a dissociation between norepinephrine, an indicator of sympathetic neural activity, and epinephrine, an indicator of adrenal medullary response. These actions may account for different metabolic and physiological responses to acute vs. chronic altitude exposure.

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Effect of beta-adrenoceptor blockade on renin-aldosterone and alpha-ANF during exercise at altitude

Journal of Applied Physiology ◽

10.1152/jappl.1989.67.1.141 ◽

1989 ◽

Vol 67 (1) ◽

pp. 141-146 ◽

Cited By ~ 23

Author(s):

P. Bouissou ◽

J. P. Richalet ◽

F. X. Galen ◽

M. Lartigue ◽

P. Larmignat ◽

...

Keyword(s):

High Altitude ◽

Sea Level ◽

Acute Mountain Sickness ◽

Plasma Renin ◽

Barometric Pressure ◽

Suppressive Effect ◽

Beta Blockade ◽

Plasma Norepinephrine ◽

Plasma Aldosterone Concentration ◽

Ergometer Exercise

The renin-aldosterone system may be depressed in subjects exercising at high altitude, thereby preventing excessive angiotensin I (ANG I) and aldosterone levels, which could favor the onset of acute mountain sickness. The role of beta-adrenoceptors in hormonal responses to hypoxia was investigated in 12 subjects treated with a nonselective beta-blocker, pindolol. The subjects performed a standardized maximal bicycle ergometer exercise with (P) and without (C) acute pindolol treatment (15 mg/day) at sea level, as well as during a 5-day period at high altitude (4,350 m, barometric pressure 450 mmHg). During sea-level exercise, pindolol caused a reduction in plasma renin activity (PRA, 2.83 +/- 0.35 vs. 5.13 +/- 0.7 ng ANG I.ml-1.h-1, P less than 0.01), an increase in plasma alpha-atrial natriuretic factor (alpha-ANF) level (23.1 +/- 2.9 (P) vs. 10.4 +/- 1.5 (C) pmol/1, P less than 0.01), and no change in plasma aldosterone concentration [0.50 +/- 0.04 (P) vs. 0.53 +/- 0.03 (C) nmol/1]. Compared with sea-level values, PRA (3.45 +/- 0.7 ng ANG I.ml-1.h-1) and PA (0.39 +/- 0.03 nmol/1) were significantly lower (P less than 0.05) during exercise at high altitude. alpha-ANF was not affected by hypoxia. When beta-blockade was achieved at high altitude, exercise-induced elevation in PRA was completely abolished, but no additional decline in PA occurred. Plasma norepinephrine and epinephrine concentrations tended to be lower during maximal exercise at altitude; however, these differences were not statistically significant. Our results provide further evidence that hypoxia has a suppressive effect on the renin-aldosterone system. However, beta-adrenergic mechanisms do not appear to be responsible for inhibition of renin secretion at high altitude.

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CATECHOLAMINE RESPONSE AT REST AND DURING EXERCISE AT SEA LEVEL, ACUTE AND CHRONIC EXPOSURE TO HIGH ALTITUDE.

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-198904001-00365 ◽

1989 ◽

Vol 21 (Supplement) ◽

pp. S61 ◽

Cited By ~ 1

Author(s):

R. S. Mazzeo ◽

G. A. Brooks ◽

J. Sutton ◽

G. Butterfield ◽

G. Wolfel ◽

...

Keyword(s):

High Altitude ◽

Sea Level ◽

Chronic Exposure ◽

Catecholamine Response ◽

Acute And Chronic Exposure

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CATECHOLAMINE RESPONSE AT REST AND DURING EXERCISE AT SEA LEVEL, ACUTE AND CHRONIC EXPOSURE TO HIGH ALTITUDE.

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-198004001-00365 ◽

1980 ◽

Vol 21 (Supplement) ◽

pp. S61

Author(s):

R. S. Mazzeo ◽

G. A. Brooks ◽

J. Sutton ◽

G. Butterfield ◽

G. Wolfel ◽

...

Keyword(s):

High Altitude ◽

Sea Level ◽

Chronic Exposure ◽

Catecholamine Response ◽

Acute And Chronic Exposure

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Alterations in enzymes involved in fat metabolism after acute and chronic altitude exposure

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.1.17 ◽

2001 ◽

Vol 90 (1) ◽

pp. 17-22 ◽

Cited By ~ 33

Author(s):

Sarah L. Kennedy ◽

William C. Stanley ◽

Ashish R. Panchal ◽

Robert S. Mazzeo

Keyword(s):

High Altitude ◽

Citrate Synthase ◽

Fat Metabolism ◽

Hypoxic Exposure ◽

Control Group ◽

Sprague Dawley ◽

Similar Reduction ◽

Altitude Exposure ◽

Cpt I ◽

Acute And Chronic Exposure

The purpose of this study was to examine the effect of acute (24 h) and chronic (5 wk) hypobaric hypoxic exposure equivalent to a simulated altitude of 4,300 m (446 mmHg) on the enzymes of fat metabolism. Heart, liver, and skeletal muscle were taken from 32 male Sprague-Dawley rats. Altitude exposure did not affect the activity of citrate synthase in any of the tissues, suggesting that mitochondrial content was unchanged. Carnitine palmitoyltransferase-I (CPT-I) activity was significantly reduced in the heart by both acute and chronic high altitude exposure compared with controls. A similar reduction was found for CPT-I activity in extensor digitorum longus after acute and chronic exposure compared with control animals. CPT-I activity was not affected by altitude exposure in the soleus muscle or the liver. 3-Hydroxyacyl-CoA dehydrogenase (β-HAD) activity was significantly depressed in the hearts of chronically exposed animals compared with controls. No difference between acute and control animals was found in the heart for β-HAD activity. Liver β-HAD activity was also significantly decreased in the acclimatized as well as in the acute animals compared with the control group. Quadriceps β-HAD activity was reduced for the chronic animals only compared with controls. These data suggest that acclimatization to high altitude selectively decreases key enzymes in fat utilization and oxidation in the heart, liver, and select skeletal muscles.

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Altitude and beta-blockade augment glucose utilization during submaximal exercise

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.2.605 ◽

1996 ◽

Vol 80 (2) ◽

pp. 605-615 ◽

Cited By ~ 93

Author(s):

A. C. Roberts ◽

J. T. Reeves ◽

G. E. Butterfield ◽

R. S. Mazzeo ◽

J. R. Sutton ◽

...

Keyword(s):

Sea Level ◽

Glucose Utilization ◽

Exercise Bout ◽

Submaximal Exercise ◽

Acute Exposure ◽

Glucose Disposal ◽

Beta Blockade ◽

Altitude Exposure ◽

Ergometer Exercise ◽

Rest And Exercise

To test the hypothesis that altitude exposure increases glucose utilization and that this increment is mediated by a beta-adrenergic mechanism, the effects of hypobaric hypoxia and beta-blockade on glucose rates of appearance (Ra), disappearance (Rd), oxidation (Rox), and leg uptake [G = 2(arteriovenous glucose difference)(1 - leg blood flow)] were measured during rest and a given submaximal exercise task. We studied six healthy beta-blocked (beta) men [26.7 +/- 1.2 (SE) yr, 74.0 +/- 6.6 kg] and five matched controls (C; 26 +/- 1.2 yr, 69.3 +/- 2.6 kg) in energy and nitrogen balance during rest and leg cycle-ergometer exercise at sea level, on acute altitude exposure to 4,300 m (barometric pressure = 463 Torr), and after 3 wk of habituation. Subjects received a primed continuous infusion of [6,6-2H]- and [1-13C]glucose, rested for = or = 90 min, and then immediately exercised for 45 min at 89 W, which elicited 49% of sea-level peak O2 consumption (VO2peak; 65% of altitude VO2peak). At sea level, resting Ra was 1.47 +/- 0.19 and 1.66 +/- 0.16 mg x kg-1 x min-1 for C and beta, respectively, and increased to 3.04 +/- 0.25 and 3.56 +/- 0.27 mg x kg-1 x min-1, respectively, during exercise. Thus glucose Ra was significantly increased by beta-blockade during rest and exercise at sea level. At sea level, beta-blockade increased leg G, which accounted for 49 and 69% of glucose disposal during exercise in C and beta, respectively. On acute altitude exposure, glucose Ra rose significantly during rest and exercise relative to sea level, whereas blockade continued to augment this increment. During exercise on acute exposure, G increased more than at sea level and accounted for a greater percentage (80 and 97%, respectively) of Rd in C and beta during exercise. Similarly, Rox values, particularly during exercise, were increased significantly at altitude relative to sea level, and beta-blockade potentiated this effect. During a given submaximal exercise task after acclimatization, glucose Ra, Rox, and G were increased relative to sea level, but these increments were less than those in response to exercise measured on acute exposure. We conclude that altitude exposure increases glucose use during rest and a given submaximal exercise bout and beta-blockade exaggerates the response.

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Catecholamine responses to α-adrenergic blockade during exercise in women acutely exposed to altitude

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.1.121 ◽

2001 ◽

Vol 90 (1) ◽

pp. 121-126 ◽

Cited By ~ 23

Author(s):

Robert S. Mazzeo ◽

Joy D. Carroll ◽

Gail. E. Butterfield ◽

Barry Braun ◽

Paul B. Rock ◽

...

Keyword(s):

High Altitude ◽

Sea Level ◽

Bicycle Ergometer ◽

Plasma Norepinephrine ◽

Adrenergic Blockade ◽

Plasma Epinephrine ◽

Exercise Tests ◽

Altitude Exposure ◽

Graded Exercise ◽

Placebo Trial

We have previously documented the importance of the sympathetic nervous system in acclimatizing to high altitude in men. The purpose of this investigation was to determine the extent to which α-adrenergic blockade affects the sympathoadrenal responses to exercise during acute high-altitude exposure in women. Twelve eumenorrheic women (24.7 ± 1.3 yr, 70.6 ± 2.6 kg) were studied at sea level and on day 2 of high-altitude exposure (4,300-m hypobaric chamber) in either their follicular or luteal phase. Subjects performed two graded-exercise tests at sea level (on separate days) on a bicycle ergometer after 3 days of taking either a placebo or an α-blocker (3 mg/day prazosin). Subjects also performed two similar exercise tests while at altitude. Effectiveness of blockade was determined by phenylephrine challenge. At sea level, plasma norepinephrine levels during exercise were 48% greater when subjects were α-blocked compared with their placebo trial. This difference was only 25% when subjects were studied at altitude. Plasma norepinephrine values were significantly elevated at altitude compared with sea level but to a greater extent for the placebo (↑59%) vs. blocked (↑35%) trial. A more dramatic effect of both altitude (↑104% placebo vs. 95% blocked) and blockade (↑50% sea level vs. 44% altitude) was observed for plasma epinephrine levels during exercise. No phase differences were observed across any condition studied. It was concluded that α-adrenergic blockade 1) resulted in a compensatory sympathoadrenal response during exercise at sea level and altitude, and 2) this effect was more pronounced for plasma epinephrine.

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Hormonal changes in normal and polycythemic high-altitude natives

Journal of Applied Physiology ◽

10.1152/jappl.1995.79.3.795 ◽

1995 ◽

Vol 79 (3) ◽

pp. 795-800 ◽

Cited By ~ 22

Author(s):

A. M. Antezana ◽

J. P. Richalet ◽

I. Noriega ◽

M. Galarza ◽

G. Antezana

Keyword(s):

High Altitude ◽

Systolic Pressure ◽

Plasma Aldosterone ◽

Control Group ◽

Protective Mechanism ◽

Hormonal Changes ◽

Plasma Aldosterone Concentration ◽

Pulmonary Arterial ◽

Exercise Induced ◽

Acute And Chronic Exposure

Acute and chronic exposure to high-altitude (HA) hypoxia inhibits the renin-angiotensin-aldosterone system and may modify the release of atrial natriuretic peptide (ANP) in sea-level (SL) natives. In HA natives, the release of these hormones could be influenced by changes in blood volume or pulmonary arterial pressure. Twenty-four men residing in La Paz, Bolivia, at 3,600 m were separated into two groups: one normocythemic (HAN; with hematocrit < 57%; n = 13) and the other polycythemic (HAP; with hematocrit > 57%; n = 11). A control group of 9 SL residents was studied in normoxia (SLN) as well as after 4 days spent at 4,350 m (SLH). The groups were tested for plasma active renin (PAR), plasma aldosterone concentration, ANP, and potassium and norepineprine concentrations at rest and after a maximal exercise. Pulmonary arterial systolic pressure was assessed by a Doppler technique. It was observed that PAR and plasma aldosterone concentration at rest and after exercise were lower in the SLH than in the SLN group. PAR and norepineprine concentration were higher among highlanders than in the SLN group. Renin response to exercise was normal among the HAN group and slightly decreased among the HAP group, and an exercise-induced increase in aldosterone was attenuated in both HA groups. Aldosterone response to renin was maintained among the SLH group but was attenuated in the HA groups, possibly owing to a protective mechanism against salt and water retention. Resting and exercise ANP was lower in the HA groups than in the SLN group.

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Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary edema

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.2.922 ◽

1996 ◽

Vol 81 (2) ◽

pp. 922-932 ◽

Cited By ~ 57

Author(s):

A. Podolsky ◽

M. W. Eldridge ◽

R. S. Richardson ◽

D. R. Knight ◽

E. C. Johnson ◽

...

Keyword(s):

Standard Deviation ◽

Pulmonary Edema ◽

High Altitude ◽

Sea Level ◽

Control Group ◽

Pulmonary Capillary ◽

High Altitude Pulmonary Edema ◽

History Of ◽

Capillary Pressures ◽

Exercise Induced

Ventilation-perfusion (VA/Q) mismatch has been shown to increase during exercise, especially in hypoxia. A possible explanation is subclinical interstitial edema due to high pulmonary capillary pressures. We hypothesized that this may be pathogenetically similar to high-altitude pulmonary edema (HAPE) so that HAPE-susceptible people with higher vascular pressures would develop more exercise-induced VA/Q mismatch. To examine this, seven healthy people with a history of HAPE and nine with similar altitude exposure but no HAPE history (control) were studied at rest and during exercise at 35, 65, and 85% of maximum 1) at sea level and then 2) after 2 days at altitude (3,810 m) breathing both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) gas at both locations. We measured cardiac output and respiratory and inert gas exchange. In both groups, VA/Q mismatch (assessed by log standard deviation of the perfusion distribution) increased with exercise. At sea level, log standard deviation of the perfusion distribution was slightly higher in the HAPE-susceptible group than in the control group during heavy exercise. At altitude, these differences disappeared. Because a history of HAPE was associated with greater exercise-induced VA/Q mismatch and higher pulmonary capillary pressures, our findings are consistent with the hypothesis that exercise-induced mismatch is due to a temporary extravascular fluid accumulation.

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