Neural Mechanisms Involved in Autonomic and Respiratory Changes in Rats,Submitted to Short-Term Sustained Hypoxia

Humans ascending to high altitudes are submitted to sustained hypoxia (SH), activating peripheral chemoreflex with several autonomic and respiratory responses. We analyzed the effect of short-term SH (24 hours, F_IO₂10%) on the cardiovascular parameters in non-anesthetized rats and on the processing of cardiovascular and respiratory reflexes using in situ and in vitro preparations. SH produced hypertension in awake rats and increased the basal sympathetic activity in an in situ preparation and these effects may be related to changes in respiratory-sympathetic coupling. SH increased both the sympatho-inhibitory and bradycardiac components of baroreflex and the sympathetic and respiratory responses of peripheral chemoreflex. Electrophysiological properties and synaptic transmission in the nucleus tractus solitarius (NTS) neurons, the first synaptic station of afferents of baro- and chemoreflex, were also evaluated using brainstem slices (in vitro studies). The second-order NTS neurons were identified by previous application of fluorescent tracer onto carotid body for chemoreceptor afferents or onto aortic depressor nerve for baroreceptor afferents. SH increased the intrinsic excitability of NTS neurons. Delayed excitation, caused by A-type potassium current (IK_A) was observed in most of NTS neurons from control rats. The IK_A amplitude was higher in identified second-order NTS neurons from control than in SH rats. SH also blunted the astrocytic inhibition of IK_A in NTS neurons and increased the synaptic transmission in response to afferent fibers stimulation. The reduction of glial cell density was also observed after SH protocol. Therefore, short-term SH produces changes in structural and functional integrity of glial cells, which are essential for neuronal activity and may contribute to the increase in cardiovascular reflex sensitivity (baro- and chemoreflex) and the development of hypertension in awake rats. Financial support: FAPESP, CAPES and CNPq.