Peripheral chemoreflex activation with potassium cyanide (KCN) in awake rats or in the working heart-brainstem preparation (WHBP) produces: (a) a sympathoexcitatory/pressor response; (b) bradycardia; and (c) an increase in the frequency of breathing. Our main aim was to evaluate neurotransmitters involved in mediating the sympathoexcitatory component of the chemoreflex within the nucleus tractus solitarii (NTS). In previous studies in conscious rats, the reflex bradycardia, but not the pressor response, was reduced by antagonism of either ionotropic glutamate or purinergic P2 receptors within the NTS. In the present study we evaluated a possible dual role of both P2 and NMDA receptors in the NTS for processing the sympathoexcitatory component (pressor response) of the chemoreflex in awake rats as well as in the WHBP. Simultaneous blockade of ionotropic glutamate receptors and P2 receptors by sequential microinjections of kynurenic acid (KYN, 2 nmol (50 nl) −1 ) and pyridoxalphosphate-6-azophenyl-2 ,4 -disulphonate (PPADS, 0.25 nmol (50 nl) −1 ) into the commissural NTS in awake rats produced a significant reduction in both the pressor (+38 ± 3 versus +8 ± 3 mmHg) and bradycardic responses (−172 ± 18 versus −16 ± 13 beats min −1 ; n = 13), but no significant changes in the tachypnoea measured using plethysmography (270 ± 30 versus 240 ± 21 cycles min −1 , n = 7) following chemoreflex activation in awake rats. Control microinjections of saline produced no significant changes in these reflex responses. In WHBP, microinjection of KYN (2 nmol (20 nl) −1 ) and PPADS (1.6 nmol (20 nl) −1 ) into the commissural NTS attenuated significantly both the increase in thoracic sympathetic activity (+52 ± 2% versus +17 ± 1%) and the bradycardic response (−151 ± 17 versus −21 ± 3 beats min −1 ) but produced no significant changes in the increase of the frequency of phrenic nerve discharge (+0.24 ± 0.02 versus +0.20 ± 0.02 Hz). The data indicate that combined microinjections of PPADS and KYN into the commissural NTS in both awake rats and the WHBP are required to produce a significant reduction in the sympathoexcitatory response (pressor response) to peripheral chemoreflex activation. We conclude that glutamatergic and purinergic mechanisms are part of the complex neurotransmission system of the sympathoexcitatory component of the chemoreflex at the level of the commissural NTS. There is both anatomical and functional evidence that the peripheral chemoreceptor afferents make their first synapses in the nucleus tractus solitarii (NTS) terminating mainly in the commissural NTS (Donoghue et al.

In the present study, we tested the hypothesis that chronic intermittent hypoxia (CIH) produces changes in the autonomic and respiratory responses to acute peripheral chemoreflex activation. To attain this goal, 3-week-old rats were exposed to 10 days of CIH (6% O 2 for 40 s at 9 min intervals; 8 h day −1 ). They were then used to obtain a working heart-brainstem preparation and, using this unanaesthetized experimental preparation, the chemoreflex was activated with potassium cyanide (0.05%, injected via the perfusion system), and the thoracic sympathetic nerve activity (tSNA), heart rate and phrenic nerve discharge (PND) were recorded. Rats subjected to CIH (n = 12), when compared with control animals (n = 12), presented the following significant changes in response to chemoreflex activation: (a) an increase in tSNA (78 ± 4 versus 48 ± 3%);

Hydrogen sulfide (H(2)S) is a gaseous neuromodulator endogenously produced in the brain by the enzyme cystathionine β-synthase (CBS). We tested the hypothesis that H(2)S acts within the anteroventral preoptic region of the hypothalamus (AVPO) modulating the production of prostaglandin (PG) E(2) (the proximal mediator of fever) and cyclic AMP (cAMP). To this end, we recorded deep body temperature (Tb) of rats before and after pharmacological modulation of the CBS-H(2)S system combined or not with lipopolysaccharide (LPS) exposure, and measured the levels of H(2)S, cAMP, and PGE(2) in the AVPO during systemic inflammation. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) did not affect basal PGE(2) production and Tb, but enhanced LPS-induced PGE(2) production and fever, indicating that endogenous H(2)S plays an antipyretic role. In agreement, icv microinjection of a H(2)S donor (Na(2)S; 260 nmol) reduced the LPS-induced PGE(2) production and fever. Interestingly, we observed that the AVPO levels of H(2)S were decreased following the immunoinflammatory challenge. Furthermore, fever was associated with decreased levels of AVPO cAMP and increased levels of AVPO PGE(2). The LPS-induced decreased levels of cAMP were reduced to a lesser extent by the H(2)S donor. The LPS-induced PGE(2) production was potentiated by AOA (the CBS inhibitor) and inhibited by the H(2)S donor. Our data are consistent with the notion that the gaseous messenger H(2)S synthesis is downregulated during endotoxemia favoring PGE(2) synthesis and lowering cAMP levels in the preoptic hypothalamus.

Laser therapy represents an effective treatment in the therapeutic arsenal of microcrystalline arthropathies.

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