The role of glycinergic inhibition in respiratory pattern formation and cardio-respiratory coupling in rats.

Cardio-respiratory coupling is reflected as respiratory sinus arrhythmia (RSA) and inspiratory-related bursting of sympathetic nerve activity. Inspiratory-related inhibitory and/or postinspiratory-related excitatory drive of cardiac vagal motoneurons (CVMs) can generate RSA. Since respiratory oscillations may depend on synaptic inhibition, we investigated the effects of blocking glycinergic neurotransmission (systemic and local application of the glycine receptor (GlyR) antagonist, strychnine) on the expression of the respiratory motor pattern, RSA and sympatho-respiratory coupling. We recorded heart-rate, phrenic, recurrent laryngeal and thoracic sympathetic nerve activities (PNA, RLNA, t-SNA) in a working-heart-brainstem preparation of rats, and show that systemic strychnine (50-200 â€‹nM) abolished RSA and triggered a shift of postinspiratory RLNA into inspiration, while t-SNA remained unchanged. Bilateral strychnine microinjection into the ventrolateral medullary area containing CVMs and laryngeal motoneurons (LMNs) of the nucleus ambiguus (NA/CVLM), the nucleus tractus solitarii, pre-Bötzinger Complex, Bötzinger Complex or Kölliker-Fuse nuclei revealed that only NA/CVLM strychnine microinjections mimicked the effects of systemic application. In all other target nuclei, except the Bötzinger Complex, GlyR-blockade attenuated the inspiratory-tachycardia of the RSA to a similar degree while evoking only a modest change in respiratory motor patterning, without changing the timing of postinspiratory-RLNA, or t-SNA. Thus, glycinergic inhibition at the motoneuronal level is involved in the generation of RSA and the separation of inspiratory and postinspiratory bursting of LMNs. Within the distributed ponto-medullary respiratory pre-motor network, local glycinergic inhibition contribute to the modulation of RSA tachycardia, respiratory frequency and phase duration but, surprisingly it had no major role in the mediation of respiratory-sympathetic coupling.

Hydrogen peroxide centrally attenuates hyperosmolarity-induced thirst and natriuresis.

Intragastric hypertonic NaCl that simulates the ingestion of osmotically active substances by food intake induces thirst, vasopressin and oxytocin release, diuresis and natriuresis. Reactive oxygen species (ROS) produced endogenously in central areas may act modulating autonomic and behavioral responses. In the present study, we investigated the effects of H2O2 injected centrally on water intake and renal responses induced by increasing plasma osmolality with intragastric (ig) administration of 2M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) with stainless steel cannula implanted in the lateral ventricle (LV) were used. Injections of H2O2 (2.5 µmol/1 µl) into the LV reduced ig 2M NaCl-induced water intake (3.1 ± 0.7, vs. PBS: 8.6 ± 1.0 ml/60 min, p<0.05), natriuresis (769 ± 93, vs. PBS: 1158 ± 168 µEq/120 min, p<0.05) and diuresis (4.1 ± 0.5, vs. PBS: 5.0 ± 0.5 ml/120 min, p<0.05). Injections of H2O2 into the LV also decreased meal associated water intake (4.9 ± 1.5, vs. PBS: 11.0 ± 1.7 ml/120 min). However, H2O2 into the LV did not modify 2% sucrose intake (3.3 ± 1.5, vs. PBS: 5.4 ± 2.3 ml/120 min) or 24h food deprivation-induced food intake (8.2 ± 2.0, vs. PBS: 11.0 ± 1.6g/120 min), suggesting that this treatment does not produce nonspecific inhibition of ingestive behaviors. The data suggest an inhibitory role for H2O2 acting centrally on thirst and natriuresis induced by hyperosmolarity and on meal-associated thirst.