Regulation of visceral sympathetic tone by A5 noradrenergic neurons in rodents

• Published in: The Journal of physiology 2011-02, Vol.589 (4), p.903-917
• Main Authors: Kanbar, Roy, Depuy, Seth D., West, Gavin H., Stornetta, Ruth L., Guyenet, Patrice G.
• Format: Article
• Language: English
• Subjects: Animals; Brain slice preparation; Carbon dioxide; Carotid body; Carotid Body - physiology; Central nervous system; Chemoreceptor Cells - physiology; Chemoreceptors (internal); Consciousness; Hypercapnia; Hypertension; Hypoxia; Male; Mice; Mice, Transgenic; Neurons; Neurons - physiology; Neuroscience; Norepinephrine; Norepinephrine - physiology; Optics; pH effects; Pons - physiology; Rats; Rats, Sprague-Dawley; Renal nerve; Rodents; Sleep; Sleep disorders; Sympathetic Fibers, Postganglionic - physiology; Sympathetic nervous system; Vasoconstriction; Viscera; Viscera - innervation; Viscera - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2010.198374

Non‐technical summary Patients suffering from obstructive sleep apnoea (OSA) experience repeated decreases in blood oxygen (hypoxia) and increases in CO2 (hypercapnia) causing sleep disruption, cardiac over‐stimulation, intense vasoconstriction and, eventually, day‐time hypertension. Hypoxia and hypercapnia initiate these responses by activating the carotid bodies whereas hypercapnia also works in the central nervous system. In this study in anaesthetized rats we show that a group of noradrenergic neurons located in the lower brainstem (A5 neurons) are vigorously activated by carotid body stimulation and mildly affected by CO2. We also show that selective activation of the A5 neurons increases sympathetic tone to the viscera and we suggest that these catecholaminergic neurons contribute to the cardiovascular stimulation caused by acute hypoxia. The importance of the A5 neurons to acute hypoxic responses in the conscious state remains to be assessed and their contribution to the day‐time hypertension associated with OSA is also a matter for future research.   The ventrolateral pons contains the A5 group of noradrenergic neurons which regulate the circulation and probably breathing. The present experiments were designed to identify these neurons definitively in vivo, to examine their response to chemoreceptor stimuli (carotid body stimulation and changes in brain pH) and to determine their effects on sympathetic outflow. Bulbospinal A5 neurons, identified by juxtacellular labelling in anaesthetized rats, had a slow regular discharge, were vigorously activated by peripheral chemoreceptor stimulation with cyanide, but only mildly activated by hyperoxic hypercapnia (central chemoreceptor stimulation). The caudal end of the A5 region also contained neurons with properties reminiscent of retrotrapezoid neurons. These cells lacked a spinal axon and were characterized by a robust response to CO2. The pH sensitivity of A5 neurons, examined in brain slices from neonatal (postnatal days 6–10) tyrosine hydroxylase (TH)‐GFP transgenic mice, was about 10 times smaller than that of similarly recorded retrotrapezoid neurons. Selective stimulation of the A5 neurons in rats using channelrhodopsin optogenetics (A5 TH neurons represented 66% of transfected cells) produced fivefold greater activation of the renal nerve than the lumbar sympathetic chain. In summary, adult A5 noradrenergic neurons are vigorously activated by carotid body stimulation. This effect presumably contri