Altered sympathetic reflexes and vascular reactivity in rats after exposure to chronic intermittent hypoxia.

Exposure to chronic intermittent hypoxia (CIH) yields persistent elevations in sympathetic nerve activity (SNA) and mean arterial pressure(MAP)with exaggerated sympathetic chemoreflexes. We examined the impact of CIH upon other sympathoexcitatory reflexes and a potential central mechanism underlying the altered regulation of SNA.Male Sprague-Dawley rats were exposed to CIH for 2 weeks (40 s at 6% O2 every 9 min, 8 h day⁻¹). After exposure to CIH, urethane-anaesthetized, vagotomized, ventilated, paralysed rats had significantly elevated MAP, splanchnic SNA, and rate of phrenic nerve discharge (PND; P<0.05). Elimination of SNA by ganglionic blockade produced a larger fall in MAP in rats exposed to CIH (P<0.05). Like acute hypoxia, stimulation of the sciatic nerve or the nasal mucosa evoked greater increases in SNA after exposure to CIH (P<0.05). In addition, acute hypoxia promoted exaggerated increases in PND amplitude after CIH (P<0.05). In contrast, the nasopharyngeal reflex evoked exaggerated increases in SNA during apnoea. These sympathoexcitatory reflexes are mediated by glutamatergic activation of the rostral ventrolateral medulla (RVLM), and accordingly, microinjections of glutamate into RVLM evoked larger increases in SNA after CIH (P<0.05). Paradoxically, none of these exaggerated acute rises in SNA was accompanied by enhanced pressor responses. Reduced adrenergic vascular reactivity may contribute to the blunted sympathetically mediated pressor responses, because bolus doses of phenylephrine evoked attenuated pressor responses after CIH (P<0.01).These data suggest exposure to CIH facilitates activation of SNA, potentially by changes within the RVLM. However, the exaggerated rises in SNA are not dependent upon stimulation of inspiratory drive. Although elevated SNA may contribute to CIH-induced hypertension, reduced adrenergic vascular reactivity buffers the cardiovascular impact of exaggerated acute rises in SNA.