Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata.
703 - 710.
Aims 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.Methods and 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 similar to 50% reduction in renal sympathetic nerve activity and a profound fall in arterial blood pressure (by similar to 25 mmHg). However, under these conditions systemic hypercapnia still evoked vigorous sympathetic activation and the slopes of the CO2-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.Conclusion 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 CO2.
|Title:||Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata|
|Keywords:||Sympathetic, Arterial blood pressure, Obstructive sleep apnoea, Hypercapnia, Lentivirus, OBSTRUCTIVE SLEEP-APNEA, CARDIOVASCULAR REGULATION, RETROTRAPEZOID NUCLEUS, CHEMOSENSORY CONTROL, NERVE ACTIVITY, RISK-FACTOR, IN-VIVO, RATS, BRAIN, PHOTOSTIMULATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics
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