RESUMO
This study evaluated the effect of blockade of the excitatory amino acid (EAA) receptors in the dorsomedial hypothalamic (DMH) area on the ventilatory and cardiovascular responses of the chemoreflex activation in conscious rats. Bilateral microinjection of kynurenic acid (2.7 nmol, n = 6) into the DMH area reduced the tachypneic (+ 264 ± 13 versus + 204 ± 14 cpm, P < 0.05) and pressor (+ 52 ± 5 versus + 31 ± 6 mmHg, P < 0.05) components of chemoreflex but had no effect on the bradycardic component (-214 ± 7 versus -244 ± 17 bpm) of the chemoreflex. The magnitudes of the reduction in pressor and tachypneic chemoreflex responses were not significantly correlated (r = 0.308, P = 0.330). These data indicate that neurons located in the DMH area are activated by chemoreflex; that this activation is mediated via EAA receptors; and that it is essential for the full expression of the respiratory component of the chemoreflex.
Assuntos
Núcleo Hipotalâmico Dorsomedial/metabolismo , Receptores de Glutamato/metabolismo , Respiração , Taquipneia/metabolismo , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Núcleo Hipotalâmico Dorsomedial/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Ácido Cinurênico/farmacologia , Masculino , Pletismografia , Cianeto de Potássio/farmacologia , Ratos , Ratos Wistar , Respiração/efeitos dos fármacos , Taquipneia/induzido quimicamente , Fatores de TempoRESUMO
The search for new nitric oxide donors is warranted by the limitations of organic nitrates currently used in cardiology. The new organic nitrate 2-nitrate-1,3-dibuthoxypropan (NDBP) exhibited promising cardiovascular activities in previous studies. The aim of this study was to investigate the cardiorespiratory responses evoked by NDBP and to compare them to the clinically used organic nitrate nitroglycerine (NTG). Arterial pressure, heart rate and respiration were recorded in conscious adult male Wistar rats. Bolus i.v. injection of NDBP (1 to 15mg/kg; n=8) and NTG (0.1 to 5mg/kg; n=8) produced hypotension. NDBP induced bradycardia at all doses, while NTG induced tachycardia at three lower doses but bradycardia at higher doses. Hydroxocobalamin (20mg/kg; HDX), a NO scavenger, blunted hypotension induced by NDBP (15mg/kg), and its bradycardic effect (n=6). In addition, HDX blunted both hypotension and bradycardia induced by a single dose of NTG (2.5mg/kg; n=6). Both NDBP and NTG altered respiratory rate, inducing a biphasic effect with a bradypnea followed by a tachypnea; HDX attenuated these responses. Our data indicate that NDBP and NTG induce hypotension, bradycardia and bradypnea, which are mediated by nitric oxide release.