Central chemoreceptors and sympathetic vasomotor outflow

摘要: In the absence of input from carotid bodies and cardiopulmonary receptors hypercapnia markedly increases sympathetic nerve discharge (SND) to heart blood vessels (Hanna et al. 1988). The effect CO2 is generally attributed following chain events: brain extracellular fluid acidification stimulates central ‘respiratory’ chemoreceptors, these chemoreceptors activate respiratory pattern generator (CPG) CPG ultimately drives generating network by phasically exciting sympathoexcitatory neurons rostral ventrolateral medulla (RVLM) (Millhorn & Eldridge, 1986; Richter Spyer, 1990; Guyenet Koshiya, 1992). This theory relies on evidence. SND activation occurs in bursts that are synchronized with cycle (Millhorn, Millhorn Habler 1994). Damage medullary surface via cooling, lesions or chemicals typically attenuates PND oscillations roughly proportional manner 1979; Millhorn, 1986). During chemoreceptor stimulation, RVLM exhibit patterns respiratory-related activity similar those barosensitive ganglionic (McAllen, 1987; Haselton Guyenet, 1989; Darnall Miyawaki 1995). However, a number assumptions underlying currently accepted view how affects have not been tested. For example, proposed circuit presumes does contain pH-responsive elements. Already challenged 25 years ago (Trzebski Kubin, 1981), this premise even less persuasive at present given recent evidence pontomedullary region may multiple sites for chemoreception (nucleus solitary tract (NTS), retrotrapezoid nucleus (RTN), pre-Botzinger complex, raphe) (Nattie Li, 1996; Feldman 2003; Hodges 2004; Mulkey Putnam Richerson 2005). Noradrenergic pH-sensitive (Pineda Aghajanian, 1997) also property they express high levels TASK channels, close relationships capillaries possess dendrites reach ventral (Milner 1987, Washburn 2003). Second, observation vasomotor rhythmic insufficient conclude cells cause increased associated stimulation. Only one study has examined whether overall actually stimulation (Haselton 1989) none their degree commensurate rise tone. Third, fact activated during mean such caused excitatory volleys neurons. Respiratory synchronous can be sculpted periodic inhibitory inputs background tonic excitation. Many group (VRG) expiratory chemosensitive RTN derive modulation fashion (Sun 2001; 2005a). same type synaptic mechanism could account since principal tonically active GABAergic caudal (CVLM) strongly modulated (Schreihofer Mandel Schreihofer, 2006). The goal experiments test several unproven underlie our understanding SND. main objectives rigorously role reflex, determine glutamate-mediated circumscribe oblongata which contains elements primarily responsible elevating