RESUMO
Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters the development of brainstem circuits that control breathing. Here, we test the hypothesis that DNE alters the respiratory motor response to endogenous and exogenous acetylcholine (ACh) in neonatal rats. We used the brainstem-spinal cord preparation in the split-bath configuration, and applied drugs to the brainstem compartment while measuring the burst frequency and amplitude of the fourth cervical ventral nerve roots (C4VR), which contain the axons of phrenic motoneurons. We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh. The main findings include: (1) atropine reduced frequency similarly in controls and DNE animals, while curare caused modest slowing in controls but no consistent change in DNE animals; (2) DNE greatly attenuated the increase in C4VR frequency mediated by exogenous ACh; (3) stimulation of nAChRs with ACh in the presence of atropine increased frequency markedly in controls, but not DNE animals; (4) stimulation of mAChRs with ACh in the presence of curare caused a modest increase in frequency, with no treatment group differences. DNE blunts the response of the respiratory central pattern generator to exogenous ACh, consistent with reduced availability of functionally competent nAChRs; DNE did not alter the muscarinic control of respiratory motor output. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1138-1149, 2016.
Assuntos
Acetilcolina/metabolismo , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Respiração , Acetilcolina/farmacologia , Animais , Animais Recém-Nascidos , Atropina/farmacologia , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/crescimento & desenvolvimento , Tronco Encefálico/metabolismo , Agonistas Colinérgicos/farmacologia , Curare/farmacologia , Modelos Animais de Doenças , Feminino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Antagonistas Muscarínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/crescimento & desenvolvimento , Nervo Frênico/metabolismo , Gravidez , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/metabolismo , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: Whether or not isolated endurance training of the respiratory muscles improves whole-body endurance exercise performance is controversial, with some studies reporting enhancements of 50% or more, and others reporting no change. Twenty fit (VO2 max 56.0 ml/kg/min), experienced cyclists were randomly assigned to three groups. The experimental group (n = 10) trained their respiratory muscles via 20, 45 min sessions of hyperpnea. The placebo group (n = 4) underwent "sham" training (20, 5 min sessions), and the control group (n = 6) did no training. RESULTS: After training, the experimental group increased their respiratory muscle endurance capacity by 12%. Performance on a bicycle time trial test designed to last about 40 min improved by 4.7% (9 of 10 subjects showed improvement). There were no test-re-test improvements in either respiratory muscle or bicycle exercise endurance performance in the placebo group, nor in the control group. After training, the experimental group had significantly higher ventilatory output and VO2, and lower PCO2, during constant work-rate exercise; the placebo and control groups did not show these changes. The perceived respiratory effort was unchanged in spite of the higher ventilation rate after training. CONCLUSIONS: The results suggest that respiratory muscle endurance training improves cycling performance in fit, experienced cyclists. The relative hyperventilation with no change in respiratory effort sensations suggest that respiratory muscle training allows subjects to tolerate the higher exercise ventilatory response without more dyspnea. Whether or not this can explain the enhanced performance is unknown.