Are C1 Neurons Involved in the Sympathetic Overactivity Induced by Chronic Intermittent Hypoxia?

Abstract

Chronic intermittent hypoxia (CIH) produces expiratory‐related sympatho‐excitation in rats, which might contribute to the development of hypertension. We evaluated the role of sympatho‐excitatory cathecolaminergic medullary C1 neurons in the CIH‐induced expiratory‐related sympatho‐excitation and hypertension in rats. In awake rats in vivo and in in situ perfused preparations of rat, C1 neurons were acutely silenced by application of the insect peptide allatostatin following cell‐specific targeting with a lentiviral vector to express the inhibitory Drosophila allatostatin receptor in control and CIH rats (10 days). In awake rats in vivo, inhibition of ~ 72% of the C1 neurons resulted in a profound and similar fall in arterial pressure and heart rate in control (n=12) and CIH rats (n=12). However, CIH rats still presented elevated arterial pressure after C1 inhibition (p<0.05). In in situ, C1 inhibition resulted in reversible reductions of perfusion pressure, amplitude of inspiratory‐related bursts of thoracic sympathetic nerve and C1 pre‐sympathetic neurons activities in control (n=7) and CIH (n=9) rats. However, CIH‐ (n=9), acute hypoxia‐ (n=7) or CO2‐induced expiratory‐related sympatho‐excitation (n=10) were not affected by C1 inhibition. These data confirm a physiological role of C1 neurons in generating baseline sympathetic activity and arterial pressure. However, C1 neurons apparently are not involved in the expiratory‐related sympatho‐excitation and hypertension induced by CIH.Support or Funding InformationFAPESP and CNPQ