PT - JOURNAL ARTICLE AU - Mieczyslaw Pokorski AU - Monika Bialkowska AU - Dominika Zajac AU - Andrea Mazzatenta AU - Camillo Di Giulio TI - Dopamine metabolism and the ventilatory response to hypoxia in the rat DP - 2014 Sep 01 TA - European Respiratory Journal PG - P1521 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/P1521.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/P1521.full SO - Eur Respir J2014 Sep 01; 44 AB - Dopamine (DA), a putative neurotransmitter at the carotid body, administered exogenously, is inhibitory for the hypoxic ventilatory response (HVR) in man and most animal species. The action of endogenous DA is less clear, but it might stimulate chemosensory discharge and consequently ventilation through low affinity D2 receptors. This study seeks to determine the ventilatory effects of enhanced availability of endogenous DA caused by inhibition of DA enzymatic breakdown. We used peripheral inhibitors of MAO, debrisoquine - 40 mg/kg, or COMT, entacapone – 30 mg/kg, and both combined, as well as the solvent DMSO as basic control, all given intraperitoneally to conscious rats. Ventilation and its responses to acute 8% O2 in N2 were investigated 30 and 60 min post-injection in a body plethysmograph. We found that inhibition of MAO-mediated degradation of DA augmented the HVR. Inhibition of COMT failed to influence the hypoxic response. However, simultaneous inhibition of both enzymes, when endogenous availability of DA should increase the most, rolled back the hypoxic ventilatory augmentation of MAO-inhibition alone. The inference is that when MAO alone is blocked, COMT takes over DA degradation, which lowers the availability of DA, resulting in a higher intensity of HVR. Thus, the findings support the notion that endogenous DA is inhibitory for HVR.