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 (CB). In ovariectomized female rats raised at sea level, domperidone, a peripheral D2 receptor antagonist, increased ventilation in normoxia (Ve : + 55%) and acute hypoxia (+ 32%). This effect disappeared after 10 daily injections of ovarian steroids (progesterone + estradiol). At high altitude (HA--3,600 m, IBBA, La Paz, Bolivia), neutered females had higher CB tyrosine hydroxylase activity (the rate-limiting enzyme for catecholamine synthesis: + 129%) and dopamine utilization (+ 150%), lower Ve (- 30%) and hypoxic ventilatory response (- 57%), and higher hematocrit (+ 18%) and hemoglobin 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.