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Am J Physiol Regul Integr Comp Physiol 282: R765-R773, 2002; doi:10.1152/ajpregu.00398.2001
0363-6119/02 $5.00
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Vol. 282, Issue 3, R765-R773, March 2002

Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats

Vincent Joseph1, Jorge Soliz2, Ruddy Soria3, Jacqueline Pequignot4, Roland Favier4, Hilde Spielvogel3, and Jean Marc Pequignot4

1 Centre d'Étude des Rythmes Biologiques, Université Libre de Bruxelles-Hôpital Erasme, B-1070 Brussels, Belgium; 2 Physiologisches Institut, Universität Zürich-Irchel, CH-8057 Zurich, Switzerland; 3 Instituto Boliviano de Biología de Altura, Embajada de Francia, La Paz, Bolivia; and 4 Laboratoire de Physiologie des Régulations Energétiques, Cellulaires et Moléculaires, Centre National de la Recherche Scientifique et Faculté de Médecine, Université Claude Bernard, Unité Mixte de Recherche 5123, F-69373 Lyon, France

We tested the hypothesis that ovarian steroids stimulate breathing through a dopaminergic mechanism in the carotid bodies. In ovariectomized female rats raised at sea level, domperidone, a peripheral D2-receptor antagonist, increased ventilation in normoxia (minute ventilation = +55%) and acute hypoxia (+32%). This effect disappeared after 10 daily injections of ovarian steroids (progesterone + estradiol). At high altitude (3,600 m, Bolivian Institute for High-Altitude Biology-IBBA, La Paz, Bolivia), neutered females had higher carotid body tyrosine hydroxylase activity (the rate-limiting enzyme for catecholamine synthesis: +129%) and dopamine utilization (+150%), lower minute ventilation (-30%) and hypoxic ventilatory response (-57%), and higher hematocrit (+18%) and Hb concentration (+21%) than intact female rats. Consistent signs of arterial pulmonary hypertension (right ventricular hypertrophy) also appeared in ovariectomized females. None of these parameters was affected by gonadectomy in males. Our results show that ovarian steroids stimulate breathing by lowering a peripheral dopaminergic inhibitory drive. This process may partially explain the deacclimatization of postmenopausal women at high altitude.

hypoxia; ovarian steroids; chronic mountain sickness


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