title: Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata.
abstract: OBJECTIVE
  Increased sympathetic tone in obstructive sleep apnoea results from recurrent episodes of systemic hypoxia and hypercapnia and might be an important contributor to the development of cardiovascular disease. In this study, we re-evaluated the role of a specific population of sympathoexcitatory catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata in the control of sympathetic vasomotor tone, arterial blood pressure, and hypercapnia-evoked sympathetic and cardiovascular responses.
  
  
  RESULTS
  In anaesthetized rats in vivo and perfused rat working heart brainstem preparations in situ, C1 neurones 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 anaesthetized rats with denervated peripheral chemoreceptors, acute inhibition of 50% of the C1 neuronal population resulted in ∼50% reduction in renal sympathetic nerve activity and a profound fall in arterial blood pressure (by ∼25 mmHg). However, under these conditions systemic hypercapnia still evoked vigorous sympathetic activation and the slopes of the CO(2)-evoked sympathoexcitatory and cardiovascular responses were not affected by inhibition of C1 neurones. Inhibition of C1 neurones in situ resulted in a reversible fall in perfusion pressure and the amplitude of respiratory-related bursts of thoracic sympathetic nerve activity.
  
  
  CONCLUSIONS
  These data confirm a fundamental physiological role of medullary catecholaminergic C1 neurones in maintaining resting sympathetic vasomotor tone and arterial blood pressure. However, C1 neurones do not appear to mediate sympathoexcitation evoked by central actions of CO(2).
authors.affiliation: Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Nephtali
authors.initials: N
authors.lastname: Marina
authors.forename: Ana P L
authors.initials: AP
authors.lastname: Abdala
authors.forename: Alla
authors.initials: A
authors.lastname: Korsak
authors.forename: Annabel E
authors.initials: AE
authors.lastname: Simms
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Allen
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Gourine
mesh_terms: D059331:Adrenergic Neurons / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000032:analysis; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D009479:Neuropeptides; C485184:enhanced green fluorescent protein; C076523:allatostatin; D002245:Carbon Dioxide; D049452:Green Fluorescent Proteins