Central chemoreceptors and sympathetic vasomotor outflow.
The present study explores how elevations in brain P(CO(2)) increase the sympathetic nerve discharge (SND). SND, phrenic nerve discharge (PND) and putative sympathoexcitatory vasomotor neurons of the rostral ventrolateral medulla (RVLM) were recorded in anaesthetized sino-aortic denervated and vagotomized rats. Hypercapnia (end-expiratory CO(2) from 5% to 10%) increased SND (97 +/- 6%) and the activity of RVLM neurons (67 +/- 4%). Injection of kynurenic acid (Kyn, ionotropic glutamate receptor antagonist) into RVLM or the retrotrapezoid nucleus (RTN) eliminated or reduced PND, respectively, but did not change the effect of CO(2) on SND. Bilateral injection of Kyn or muscimol into the rostral ventral respiratory group (rVRG-pre-Bötzinger region, also called CVLM) eliminated PND while increasing the stimulatory effect of CO(2) on SND. Muscimol injection into commissural part of the solitary tract nucleus (commNTS) had no effect on PND or SND activation by CO(2). As expected, injection of Kyn into RVLM or muscimol into commNTS virtually blocked the effect of carotid body stimulation on SND in rats with intact carotid sinus nerves. In conclusion, CO(2) increases SND by activating RVLM sympathoexcitatory neurons. The relevant central chemoreceptors are probably located within or close to RVLM and not in the NTS or in the rVRG-pre-Bötzinger/CVLM region. RVLM sympathoexcitatory neurons may be intrinsically pH-sensitive and/or receive excitatory synaptic inputs from RTN chemoreceptors. Activation of the central respiratory network reduces the overall sympathetic response to CO(2), presumably by activating barosensitive CVLM neurons and inhibiting RTN chemoreceptors.
Moreira
Thiago S
TS
Department of Pharmacology, University of Virginia, Charlottesville, VA, 22908, USA.
Takakura
Ana C
AC
Colombari
Eduardo
E
Guyenet
Patrice G
PG
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011659:Pulmonary Gas Exchange / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology*; D014666:Vasomotor System / Q000502:physiology*
D002245:Carbon Dioxide