Comp. Biochem. Physiol. Vol. 118A, No. 1, pp. 1–7, 1997 ISSN 0300-9629/ 97/$17.00 Copyright  1997 Elsevier Science Inc. PII S0300-9629(96)00369-6 Peripheral Chemosensitivity and Central Integration: Neuroplasticity of Catecholaminergic Cells Under Hypoxia V. Soulier, 1 C. Gestreau, 2 N. Borghini, 2 Y. Dalmaz, 1 J. M. Cottet-Emard, 3 and J. M. Pequignot 1 1 UMR 5578 CNRS, 3 Laboratoire de Physiologie de l’Environnement, Universite ´ Claude Bernard, 69373 Lyon Cedex 08, France, and 2 URA 1832 CNRS, De ´partement de Physiologie et Neurophysiologie, Universite ´ Aix-Marseille III, 13397 Marseille Cedex 20, France ABSTRACT. The plasticity of catecholaminergic cells within the carotid body, brainstem and sympatho-adre- nal system was analyzed in rats subjected to normobaric hypoxia (10% O 2 ) lasting up to 3 weeks. Long-term hypoxia elicited structural, neurochemical and phenotypic changes in carotid body and sympathetic ganglia (SIF cells), and stimulated the norepinephrine turnover in A2 neurons located caudal to the obex, the area where the chemosensory nerve fibers end. Chemodenervation abolished central alterations. Adaptive mechanisms for increasing norepinephrine biosynthesis in hypoxia involved changes in activity of pre-existing tyrosine hydroxy- lase, the rate-limiting enzyme of catecholamine biosynthesis, and induction of new tyrosine hydroxylase protein. These neurochemical changes occurred after sustained hypoxia only, suggesting that noradrenergic neurons are involved in the central chemoreceptor pathway during sustained hypoxia but are not essential for regulatory responses to acute hypoxia. Acute hypoxia elicited the expression of c-Fos protein in neurons located in nucleus tractus solitarius that were not catecholaminergic. Noradrenaline released under long-term hypoxia could play a neuromodulatory role in ventilatory acclimatization. Cardiovascular responses to hypoxia are mediated by changes in sympatho-adrenal outflow, different according to the target organ. Cardiac sympathetic output and adrenal secretion were stimulated independently of carotid body chemoafferents. Early postnatal hypoxia induced long-term neurochemical changes in carotid body, brainstem and sympathetic efferents that may reveal alter- ations in development of neurons involved in the chemoreceptor pathway. comp biochem physiol 118A;1: 1–7, 1997.  1997 Elsevier Science Inc. KEY WORDS. Brainstem, carotid body, dopamine, SIF cells, autonomic nervous system, long-term hypoxia, neonate, nucleus of the tractus solitarius INTRODUCTION cal or pathological processes. Actually, the fetus lives in a hypoxemic environment that is severely enhanced during Chronic hypoxia is a relatively common situation that may delivery. After birth a sustained hypoxia may occur in new- occur either in physiological or pathophysiological circum- borns and induce persistent cardiorespiratory and locomotor stances in adults and newborns. Although sojourning at disorders (23,34,38,39,57). Thus, neonatal hypoxia may high altitude is the most common physiological situation produce serious sequelae and, in particular, has been recog- in adulthood, intermittent or chronic hypoxemia may occur nized as a factor associated with sudden infant death syn- at low altitude levels, being induced by several illnesses such drome. as obstructive chronic bronchitis, cyphoscoliosis and sleep Physiological adaptive responses to long-term hypoxia in- apneas. The perinatal period is also a stage of life when volve hyperventilation in particular and increased cardiac chronic hypoxia can be observed in response to physiologi- output dependent on circulating catecholamines and auto- nomic nerve fibers. Low blood pressure in oxygen is primar- This paper was presented at the European Society of Comparative Physiol- ily sensed by peripheral arterial chemoreceptors, the most ogy and Biochemistry Symposium on ‘‘Life in Extreme Environments’’ un- important of which are the carotid bodies. Stimulation of der the theme of ‘‘Hypoxia,’’ held in June 1995 at La Seyne-sur-Mer, carotid body chemoreceptors elicits an increase in firing rate France. Address reprint requests to: J. M. Pequignot, Laboratoire de Physiologie, of chemosensory neurons whose fibers course in the carotid Faculte ´ de Me ´decine Grange-Blanche, 8, Avenue Rockefeller, 69373 sinus nerve and terminate in the nucleus tractus solitarius Lyon Cedex 08, France. Tel. 33-478-77-70-57; Fax 33-478-77-71-75; within the brainstem. Despite the importance of subsequent E-mail: pequignot@rockefeller1.univ lyon1.fr. Received 14 December 1995; accepted 14 May 1996. central integration of chemosensory inputs in influencing