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Adrenergic System in High Altitude Residents A. M. A Antezana, ntezana, J. P. Richalet, G. Antezana, Antezana, H. H. Spielvo Spielvogel, gel. R. Kacimi Kacimi Association pour la Recherche en Physiologic Physiologie de l'Environnement, 74 rue Marcel Cachin, Bobigny, France Instituto Boliviano de Biologia Bio]ogia de Altura, La Paz, Bolivia

A. M. Antezana, J. P. Richalet, G. Antezana, H. Spielvogel, R. Kacimi, Adrenergic System in High Altitude Residents. mt J Sports Mcd, Med, Vol 13, Suppl Suppi 1, pp 596— S96— SlO0, 1992. Sl00,

Heart rate (HR) response to isoproterenol (ISO) infusion (IP) is decreased in normal sea level (SL) natives exposed to high altitude (HA). Since norepinephrine

plasma concentration is higher in HA hypoxia, a downregulation of downregulation of beta-adrenoceptors beta-adrenoceptors(JEIAR) (I3AR) was was evoked. We explored this phenomenon at 3600 m in a HA normal population (HAN) and in polycythemic subjects (HAP). Results are compared to SL natives in normoxia (SLN), and during chronic hypoxia at 4800 m rn (SLH) (J Appl AppI Physiol Physiol 65: 1957—1961, 1988). ISO dose required to raise HR by 25

min1 (I 25) is not different in HAN or HAP group when compared to SLN. Density Density of of I3AR 3AR on on lymphocytes lymphocytes was was 39% and 25% lower in HAN and HAP than in SLN group, respectively. Chronotropic response to IP is similar in SL and HA subjects under their usual environmental conditions, while SL natives show a blunted response under hypoxia, probably due to a decrease decrease in in I3AR lIAR density. No

adrenergic desensitization was found in highlanders. Lower I3AR lIAR density density in in HA HA groups groups could be an adaptive mechanism to chronic hypoxia. Polycythemia does not affect this responsiveness. Key words

Hypoxia, beta-adrenergic Hypoxia, beta-adrenergic receptors, isoproterenol, norepinephrine

a blunted response to isoproterenol infusion was found (20), supporting the hypothesis of a chronotropic refractoriness secondary to increased sympathetic activity (21). A decrease in beta-adrenoceptors (I3AR) density was observed in rat cardiomyocytes (27) and in human lymphocytes exposed to altitude downregulation phenomenon phenomenon was was theretherehypoxia (25). A I3AR 3AR downregulation fore evoked. However, in highianders highlanders living under chronic hypoxic conditions no data upon adrenergic system is avilable. The purpose purpose of of this this study study was was to to evaluate evaluate this this system system in in normal normal The

and polycythemic highlanders highianders at 3600 m and to establish whether the the hypoxia-induced hypoxia-induced alterations alterations in in adrenergic adrenergic system system whether observed in sea level natives exposed to acute and chronic high altitude hypoxia are also present in this population; moreover, does does polycythemia influence this system? Finally Finally some some people people residing at this altitude and suffering from heart diseases could

also benefit from this knowledge by a rational use of beta blocker therapy. The population of high altitude residents was

compared with normal sea level level subjects subjects in in normoxia normoxia and and under hypoxic conditions (25). Methods

Twenty four men, born at 3500—4000 m (Bolivia) volunteered in this study. Group 1: 13 high altitude natives (HAN), (23—40 yrs old), with hematocrit (Ht) 57%; Group 2: 11 high altitude natives (HAP), (16—45 yrs old), with Ht >57%. 57%.AAcontrol Ht> controlgroup groupincluded included99 sea sea level level natives (28—50 (28—50 yrs old), in normoxia (SLN) and after 21 days at 4800 m (SLH). Clinical examination, complete blood count, I12-lead 2-lead electro-

cardiogram and echocardiography-Doppler were performed. Spirometric measurements measurements were were performed performed in in group group 2. 2.

Exercise testing Experiments took place at the Instituto Bolivi-

ano de Biologia de Altura (I.B.B.A.) at 3600 m (La Paz, Introduction Altitude hypoxia stimulates the adrenergic system as indicated by the increased plasma norepinephrine con-

centrations (10, 12, 19). Heart rate (HR) at rest and during

moderate exercise is increased in altitude; maximal HR HR decreases above above 3000 3000m m(9, (9,15, 15,23, 23,26). The relationship relationship clearly decreases 26). The

between HR and NEp is modified in altitude with a progressive decrease in HR for the same level of plasma NEp (24). A blunted cardiac chronotropic response at high altitude (HA)

has been demonstrated in animals under beta-adrenergic

Bolivia). Barometric pressure was 498—502 mmHg. Ambient temperature was 17—18 °C. °C. Exercise Exercise was was performed performed in in the the morning after a light breakfast. An ear oximeter was placed on ear lobe for for the the recording recording of of oxygen oxygen saturation; saturation; an intravenous earlobe cannula was inserted in the left forearm for blood sampling at rest and after exercise. Heart rate and blood pressure were continuously monitored by means of an electrocardiograph and a

manual sphygmornanorneter. sphygmomanometer. Exercise was performed on on aa mechanical cycloergometer until exhaustion. Ventilation was measured at the end of each work load; exhaled gas gas was was colcollected lected in in Douglas Douglas bags bags for for maximal maximal oxygen oxygen consumption consumption dedeterminations (Servomex analyser 570 A). Blood samples were

stimulation. In humans exposed to 4350 m during several days

drawn and centrifuged immediately for norepinephrine, epinephrine and electrolytes dosage. Plasma was stored in

lnt.J.SportsMed. Int.J.SportsMed. 13(1992)S96—S100 Georg Thieme Verlag Stuttgart New York GeorgThieme StuttgartNew

liquid nitrogen until analysis by a radioenzymatic assay (25).

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Abstract

mt. J. Sports Med. 13(1992) S97

Adrenergic System in High Altitude Residents n saturation and oxygen consumption at exercise. Tab'e 1 Heart rate, oxyge Table oxygen SLN

SLH SLH

HAN

HAP

9

9

12

11

n

age (yrs)

Ht(%) HR (min1) Sa02 (%) Sa02 (%)

rest exer

4

35 45 75 75

4

35 57

86

180

4' 4* 7* 7'

85 85

95

80

18.0±0.8 40

20.0± 1.2* 35 55

9 + 5*

61

70

8

173

94 90

4

0.7*

24.4± 1.1* +

6*

31

6*

91

2 4' 4*

21.1 21.1

32

94

97

exer exer

VO2max

34

181

171

rest

Ca02 (mI/dI) Ca02 (ml/d)

77 33

31 31 52 72

4 8

4* 4*

Ht = hematocrit, HR HR == heart heart rate, rate, Sa02 Sa02 == arterial arterialoxygen oxygensaturation, saturation,Ca02 Ca02==calcu!ated calculatedarterial arterial02 02content. content.\iO2rrlax V02rnax==maximat maximal02 02conconsumption (ml .kg kgmin'), min1), SLN SLN= =sea sealevel levelnatives nativesininnormoxia, normoxia,SLH SLH==sea sealevel levelnatives nativesininhypoxia, hypoxia,HAN HAN==high highaltitude altitudenormocythemic normocythemic nana high altitude polycythemic natives. tives, HAP

Adrenergic system in high altitude residents.

Heart rate (HR) response to isoproterenol (ISO) infusion (IP) is decreased in normal sea level (SL) natives exposed to high altitude (HA). Since norep...
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