O-2-sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cells

Ventilatory responses to acute and long-term hypoxia are classically trigge red by carotid chemoreceptors. The chemosensory inputs are carried within t he carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brains tem neurons or secondarily via carotid body inputs, we tested the ventilato ry responses to acute and long-term hypoxia in rats with bilaterally transe cted carotid sinus nerves and in sham-operated rats. Because brainstem cate cholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyros ine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in s itu hybridization and hypoxic ventilatory responses were measured in vivo b y plethysmography. After long-term hypoxia, TH mRNA levels in the nucleus t ractus solitarius and ventrolateral medulla increased similarly in chemoden ervated and sham-operated rats. Ventilatory acclimatization to hypoxia deve loped in chemodenervated rats, but to a lesser extent than in sham-operated rats. Ventilatory response to acute hypoxia, which was initially low in ch emodenervated 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 adjustm ents to hypoxia occurred independently of carotid chemosensory inputs. O-2- sensing mechanisms unmasked by carotid chemodenervation triggered two venti latory adjustments: (i) a partial acclimatization to long-term hypoxia asso ciated with TH upregulation; (ii) a complete restoration of acute hypoxic r esponsivity independent of TH upregulation.