title: Inhibition of peripheral dopamine metabolism and the ventilatory response to hypoxia in the rat.
abstract: Dopamine (DA) is a putative neurotransmitter in the carotid body engaged in the generation of the hypoxic ventilatory response (HVR). However, the action of endogenous DA is unsettled. This study seeks to determine the ventilatory effects of increased availability of endogenous DA caused by inhibition of DA enzymatic breakdown. The peripheral inhibitor of MAO - debrisoquine, or COMT - entacapone, or both combined were injected to conscious rats. Ventilation and its responses to acute 8 % O(2) in N(2) were investigated in a whole body plethysmograph. We found that inhibition of MAO augmented the hyperventilatory response to hypoxia. Inhibition of COMT failed to influence the hypoxic response. However, simultaneous inhibition of both enzymes, the case in which endogenous availability of DA should increase the most, reversed the hypoxic augmentation of ventilation induced by MAO-inhibition. The inference is that when MAO alone is blocked, COMT takes over DA degradation in a compensatory way, which lowers the availability of DA, resulting in a higher intensity of the HVR. We conclude that MAO is the enzyme predominantly engaged in the chemoventilatory effects of DA. Furthermore, the findings imply that endogenous DA is inhibitory, rather than stimulatory, for hypoxic ventilation.
authors.affiliation: Department of Respiratory Research, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Bialkowska
authors.forename: Dominika
authors.initials: D
authors.lastname: Zajac
authors.forename: Andrea
authors.initials: A
authors.lastname: Mazzatenta
authors.forename: Camillo
authors.initials: C
authors.lastname: Di Giulio
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Pokorski
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000503:physiopathology*; D002394:Catechol O-Methyltransferase / Q000502:physiology; D065098:Catechol O-Methyltransferase Inhibitors / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D003647:Debrisoquin / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D004357:Drug Synergism; D006985:Hyperventilation / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008995:Monoamine Oxidase / Q000502:physiology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010993:Plethysmography, Whole Body; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D008996:Monoamine Oxidase Inhibitors; D009570:Nitriles; C071192:entacapone; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine; D003647:Debrisoquin