Integration of the Proprioceptive and Central Inspiratory Inhibitory Afferent Inputs by Pontine Noradrenergic A5 Neurons in Rats.

Inhibitory afferent inputs to pontine A5 noradrenergic neurons (A5 NN) are not known, except partial baroreceptor input. In spontaneously breathing pentobarbital-anesthetized rats, we registered 35 A5 NN that were activated by hypoxia (100% N2, 10 sec) by more than 5 times in comparison with the background. Cooling of retrotrapezoid nucleus (15°C, 6 sec) completely blocked the motor inspiratory output and A5 NN discharge frequency increased (23/23) by more than 7 times in comparison with the background values. The beginning of A5 NN activation coincided with cessation of inspiratory activity. Short-term passive stretching of the shin muscles (1 sec, 100 g) caused BP drop and complete inhibition of A5 NN (12/12) activated by hypoxia. Inhibitory afferent inputs from proprioceptors and central inspiratory neurons that can limit A5 NN activity were demonstrated.

NMDA Receptors of A5 Area in the Regulation of Blood Pressure and Respiratory Activity during Hypoxia in Rats.

In narcotized (40 mg/kg sodium ethaminal intraperitoneally) spontaneously breathing albino rats, experimental short-term hypoxia induced BP drop and increased phrenic nerve firing rate. Unilateral microinjection of a selective NMDA receptor blocker ketamine hydrochloride (50 nl; 4 mM) into A5 area did not affect BP and phrenic nerve fi ring rate. However, against the background of preliminary NMDA receptor blockage, hypoxia more markedly stimulated rhythmic activity of the respiratory center and hypotensive response. Unilateral microinjection of a selective blocker of non-NMDA receptors GAMS (50 nl; 4 mM) into A5 area did not change initial BP and phrenic nerve fi ring rate. The studied parameters in rats exposed to hypoxia after blockage of non-NMDA receptors in A5 area did not differ from the control levels. Thus, activity of the respiratory center and BP in rats during hypoxia is regulated by the structures in A5 area and NMDA glutamate receptors.

Role of NMDA- and non-NMDA subtypes of glutamate receptors in A5 neuronal structures in the regulation of respiration and circulation during thermal nociceptive stimulation in rats.

In narcotized albino rats, thermal nociceptive stimulation elevated systemic blood pressure and increased the frequency of respiratory rhythm generation. Unilateral microinjection of ketamine hydrochloride, a selective blocker for NMDA receptors, into A5 region did not change the baseline parameters of multineuronal activity in the phrenic nerve and systemic blood pressure. Under conditions of NMDA-receptor blockade, thermal nociceptive stimulation evoked more pronounced respiratory response (in comparison to that observed before ketamine treatment), but induced smaller blood pressure rise. Unilateral microinjection of GAMS, a selective blocker for non-NMDA receptors, into A5 region did not modify the examined baseline parameters and the nociceptive response. It is concluded that during thermal nociceptive stimulation, activity of the respiratory center and blood pressure in rats are controlled by neuronal structures in A5 region via NMDA subtype of glutamate receptors.

Control of respiratory and hypotensive response during hypoxic chemoreflex by A5 region neurons in rats.

The responses of A5 region neurons, the phrenic nerve, and systemic blood pressure to short-term hypoxia were examined in rats under conditions of spontaneous respiration. Tonic and respiration-modulated neurons increasing their discharge activity during hypoxia were identified. This hypoxia-induced response was more pronounced in the neurons with baseline discharge rate of 0.1-4.5 Hz (electrical activity of neurons increased by 4-5 times) compared to neurons with the baseline activity of 5.4-49.6 Hz (discharge rate increased by 1.4-2.0 times). The latency and duration of activation of all types A5 neurons correlated with the parameters of activation of the phrenic nerve. During hypoxia, activation of A5 neurons corresponded to the period of blood pressure drop (one-third of the reaction time), but not to the period of plateau or recovery phase. Low-, middle, and high-frequency A5 neurons participated in the modulation of hypoxia-provoked respiratory and hypotensive responses. Modulation of the respiratory response by A5 neurons was observed during the entire period of phrenic nerve activation, while modulation of the hypotensive response occurred only during blood pressure decrease.

Nitric oxide in the A5 region modulates reaction of the respiratory center and blood pressure to hypoxia in rats.

Hypoxia was followed by more pronounced activation of the respiratory center and pronounced hypotensive response after unilateral injection of nitric oxide synthase blocker L-NAME into the A5 region. Microinjection of exogenous nitric oxide donor sodium nitroprusside into the A5 region abolished the effect of L-NAME on hypoxia-induced changes in activity of the respiratory center and blood pressure. Bilateral transection of the vagal and sinocarotid nerves suppressed the response of the respiratory center to hypoxia. However, the hypotensive response to hypoxia in these rats did not differ from that in intact animals. Under conditions of peripheral chemoreceptor deafferentation, the hypotensive response to hypoxia did not differ before and after blockade of nitric oxide synthase in the A5 region. The regulation of respiratory center activity and blood pressure during hypoxia was modulated by A5 neurons with the involvement of nitric oxide.

Spectral parameters of phrenic nerve activity in mature rats during electrical stimulation of retrotrapezoid nucleus.

In mature rats, electrical stimulation of the retrotrapezoid nucleus increased the amplitude and frequency of the high-frequency peak in the firing spectrum of the phrenic nerve, while the amplitude of medium-frequency peak and the amplitude ratio of medium- to high-frequency peaks decreased. These changes in spectral parameters were associated with accelerated increase in central inspiratory activity, decreased amplitude of phrenic nerve firing, and increased frequency of respiratory rhythm. It is hypothesized that being a relay structure of central chemosensitive mechanism, the retrotrapezoid nucleus regulates parameters of medium- and high-frequency spectral peaks of efferent electrical activity in the respiratory center together with the dorsal and ventral respiratory groups.

Involvement of rostral ventromedullar neuronal structures in nitric oxide modulation of central chemosensitive drive.

Surface perfusion of the rostral ventromedullar cerebral subdivisions with artificial cerebrospinal fluid containing exogenous NO donor sodium nitroprusside (0.1 mM) increased the discharge rate of the phrenic nerve and potentiated the response of the respiratory center to hypercapnia in narcotized mature rats. The latter reaction was prevented by blockage of NO-synthase in rostral ventromedullar neural structures with N(omega)-nitro-L-arginine methyl ester (L-NAME, 0.3 mM). It was hypothesized that rostral ventromedullar neural structures are involved in modulatory action of NO on central chemosensitive drive.

The involvement of rostral ventromedullary neuronal structures in regulating the mechanism of formation of the respiratory rhythm in rats.

The role of neuronal structures in the rostral parts of the ventral surface of the medulla oblongata of the rat in regulating the central inspiratory activity of the respiratory center was analyzed. It is suggested that neuronal structures of the subretrofascial area, located close to the ventral surface of the medulla oblongata have direct associations with the mechanisms generating and regulating the respiratory rhythm. These have excitatory effects on neurons of the respiratory center which generate inspiratory activity.

[Participation of rostral ventral medullary neuron structures in the regulation of the respiratory rhythm mechanism in rats]. / Uchastie rostral'nykh ventromedulliarnykh neironnykh struktur v reguliatsii mekhanizma formirovaniia dykhatel'nogo ritma u krys.

The role of neuronal structures of the rostral ventromedullary area in regulation of central inspiratory activity, was studied. The data obtained suggests that the structures of subretrofacial area are important for the respiratory rhythm generation due to regulation of excitability of the inspiratory neurons.