title: Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats.
abstract: 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.
authors.affiliation: Centre d'Etude des Rythmes Biologiques, Université Libre de Bruxelles-Hôpital Erasme, B-1070 Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Joseph
authors.forename: Jorge
authors.initials: J
authors.lastname: Soliz
authors.forename: Ruddy
authors.initials: R
authors.lastname: Soria
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Pequignot
authors.forename: Roland
authors.initials: R
authors.lastname: Favier
authors.forename: Hilde
authors.initials: H
authors.lastname: Spielvogel
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Pequignot
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D000531:Altitude; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012146:Rest
chemical_list: D002395:Catecholamines; D006454:Hemoglobins; D011374:Progesterone; D004958:Estradiol; D004294:Domperidone; D004298:Dopamine