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.

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.

[Respiratory effects of bombesin at the level of pre-Botzinger complex in rats].

Respiratory effects of 0.1 pM - .1 mM bombesin microinjected to the pre-Botzinger complex were studied in anaesthetised rats. Bombesin induced an increase in minute ventilation, respiratory frequency, a decrease in expiratory duration and shortening of inter-burst intervals on the EMG of diaphragm and external intercostal muscles. The responses to bombesin characterised by short latency, quick development (with the maximum in 3-minutes after microinjection) and found to be reversible. The effects of bombesin on membrane potential, input resistance and pattern of spontaneous activity ofpre-Botzinger neurons were investigated in brainstem slices. 1 nM bombesin introduced into the perfusion solution in most cases (68%) induced membrane depolarisation, an increase in input resistance and in spike activity of spontaneously active cells. The data obtained suggest that the respiratory effects ofbombesin at the level ofpre-Botzinger complex are caused by its action on the membrane of neurons.

Respiratory reactions to microinjection of bombesin into the solitary tract nucleus and their mechanisms.

Acute experiments were performed on urethane-anesthetized adult laboratory rats to investigate the effects of microinjections of 10(-13)-10(-4) M bombesin into the solitary tract nucleus on measures of respiration. Bombesin microinjections were found to stimulate respiration, inducing significant increases in the level of pulmonary ventilation, increases in respiratory volume, and increases in the bioelectrical activity of the inspiratory muscles. The most marked respiratory reactions were seen after intermediate peptide doses (10(-10)-10(-7) M). These respiratory effects of bombesin were found to result from its ability to suppress the inspiration-inhibiting Hering-Breuer reflex at the level of the solitary tract nucleus. The fact that ultralow doses of bombesin were active, along with the distribution of endogenous bombesin and its specific receptors in the solitary tract nucleus, and the ability of this peptide to modulate the Hering-Breuer reflex all provide evidence that bombesin is involved in controlling respiration at the level of the dorsal structures of the respiratory center.

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.

[respiratory responses to microinjections of bombesin into the solitary tract nucleus, and the mechanism of their realization].

We investigated the respiratory effects of 10-(13)-10(-4) M bombesin microinjected into the solitary tract nucleus of adult anaesthetized rats. Bombesin markedly increased ventilation, tidal volume and electric activity of inspiratory muscles. The respiratory response was most pronounced when bombesin administered in mean concentrations (10(-10)-10(-7) M). We found that the respiratory effects ofbombesin could be based on its capacity for inhibition of Hering-Breuer inspiratory termination reflex at the level of the solitary tract nucleus. These results in aggregate with pattern of the distribution of endogenous bombesin and its receptors in the solitary tract nucleus area suggest the involvement of bombesin in the respiratory control via dorsal structures of the respiratory center.