further exploration of the cellular and molecular basis of acclimatization responses in various
tissues and at various developmental ages.
144.
FETAL CEREBROVASCULAR ACCLIMATIZATION RESPONSES TO CHRONIC
HYPOXIA: A MODEL FOR PRENATAL PROGRAMMING OF ADULT DISEASE?.
Lawrence D. Longo
1
. Center for Perinatal Biology, Loma Linda University School of Medicine,
Loma Linda, California
1
.
Background: In response to high altitude chronic hypoxia, cerebral arteries of the sheep show
significantly decreased responses to both K+ -depolarization and norepinephrine-induced
contraction. The subcellular basis of these alterations is unknown. Results. For cerebral arteries in
general, high altitude hypoxia is associated with augmented or upregulation of presynaptic
functions, including response to perivascular (i.e., sympathetic) nerve stimulation. In contrast,
postsynaptic signal transduction functions, particularly those of the Ca2+ -dependent contractile
pathway such as alpha1 adrenergic receptor density, inositol 1,4,5-triphosphate responses, and
inositol 1,4,5-triphosphate receptor density tend to be significantly depressed or downregulated.
In addition, elements of the Ca2+ -independent contraction pathway, which modulate
contractions in an inhibitory manner, tend to be upregulated. These include the mitogen-activated
protein kinases, extracellular signal-regulated kinases, and other proteins/enzymes. The results
emphasize the role of chronic hypoxia in modulating signal transduction mechanisms in the
cerebral vasculature. Conclusions. In response to acclimatization, results of the present study
highlight the independent regulation of various elements of the signal transduction cascade in
cerebral vasculature. For the fetus, the results also emphasize the potential for chronic hypoxia to
"program" various tissues and organs for the development of cerebrovascular, cardiac, and other
disease as an adult.
145.
ADAPTATION TO ALTITUDE AT REST AND DURING EXERCISE IN WELL TRAINED
CLIMBERS. Are Løset
1
, Arnt Honnaas
1
, Arnt Mamen
2
, Ulrik Wisloff
1
, Alf O. Brubakk
1
. ISB,
Norwegian University of Science and Technology, Trondheim, Norway
1
, Physical Education,
Sogn Fjordane University College, Sogndal, Norway
2
.
Reduced oxygen pressure at high altitude changes both metabolic and respiratory variables in
man. However, few studies have determined the acclimatization at rest and during submaximal
exercise during ascent and adaptation to altitude in actual climbs. The main objective of this study
was to examine the effects of different altitudes on O2 consumption (VO2), O2 saturation
(SaO2), substrate oxidation and lung ventilation at rest and during submaximal exercise. The
study was performed during an ascent of Acancagua, Chile. Seven well trained (VO2max 67.9 ±
4.9 ml/kg/min) male climbers were examined at rest and during a submaximal exercise at a
steady-state workload corresponding to 35-40 % of maximal O2 uptake (VO2max) at 700 m,
2850 m, 3300 m, 4300 m and 4900 m during ascent and at 4300 m after being at the summit. At
rest, minute ventilation (VE) was 23% higher at 4300 meters compared to baseline (14.3±0.9 vs
11.6±1.7 l/min, P<0.01). SaO2 decreased at all altitudes compared to baseline and but increased
slightly (3.5%) from the 1st to the 6th day at 4300 m (84.6± 4.4 vs 87.6 ±3.1, P<0.05), however
still below baseline. During steady-state submaximal exercise, VE at 4300 m increased by 28 %
compared to baseline (54±14 vs. 42±6 l·min-1, P<0,05), while VO2 during submaximal exercise
decreased at 4300 m compared to baseline (23.9±1.2 vs. 21.7±2.1 ml·min-1·kg-1, P<0.01), before
increasing to baseline values again at 4900 m (23.9±3.2 ml·min-1·kg-1, P<0.01). Substrate
oxidation (RER) during submaximal exercise showed a significant reduction (28 %) in values
from baseline to 4300m. In summary, during ascent to high altitude there is an increase in VE.
The accompanying decrease in SaO2 at rest and during submaximal exercise is reversed during
stay at altitude. On ascent from 4300 to 4900, the VO2 during exercise is increased. There was a
reduced carbohydrate oxidation and increased fat oxidation during acclimatization to altitude.
