O2-sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cells

• Published in: The European journal of neuroscience Vol. 12; no. 9; pp. 3181 - 3190
• Main Authors: Roux, Jean-Christophe, Pequignot, Jean-Marc, Dumas, Sylvie, Pascual, Olivier, Ghilini, Ginette, Pequignot, Jacqueline, Mallet, Jacques, Denavit-Saubié, Monique
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2000; Wiley
• Subjects: Adaptation, Physiological; Adaptation, Physiological - physiology; Animals; Anoxia; Autonomic Denervation; Carotid Body; Carotid Body - physiology; Carotid Sinus; Carotid Sinus - innervation; Catecholamines; chemoreception; Chemoreceptor Cells - physiology; Chemoreceptors; Gene Expression Regulation, Enzymologic; Hypoxia - metabolism; Hypoxia - physiopathology; Life Sciences; Male; Neurons; Neurons - enzymology; Neurons and Cognition; nucleus tractus solitarius; Oxygen; Oxygen - blood; Plethysmography; rat; Rats; Rats, Sprague-Dawley; Respiration; Respiratory Center; Respiratory Center - cytology; Respiratory Center - metabolism; RNA, Messenger; RNA, Messenger - analysis; Solitary Nucleus; Solitary Nucleus - cytology; Solitary Nucleus - metabolism; Tidal Volume; Tyrosine 3-Monooxygenase; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; ventilatory acclimatisation
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.2000.00208.x

Ventilatory responses to acute and long‐term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long‐term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham‐operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long‐term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham‐operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham‐operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long‐term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2‐sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long‐term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation.