title: Heart rate response to hypoxic exercise: role of dopamine D2-receptors and effect of oxygen supplementation.
abstract: This study examined the effects of dopamine D(2)-receptor blockade on the early decrease in maximal heart rate at high altitude (4559 m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed two consecutive maximal exercise tests, without and with oxygen supplementation respectively, at sea level and after 1, 3 and 5 days at altitude. On each study day, domperidone (30 mg; n=6) or no medication (n=6) was given 1 h before the first exercise session. Compared with sea level, hypoxia progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no effect on maximal heart rate. On each study day at altitude, oxygen breathing completely reversed the decrease in maximal heart rate to values not different from those at sea level. In conclusion, dopamine D(2)-receptor blockade with domperidone demonstrates that hypoxic exercise in humans activates D(2)-receptors, resulting in a decrease in circulating levels of noradrenaline. However, dopamine D(2)-receptors are not involved in the hypoxia-induced decrease in the maximal heart rate. These data suggest that receptor uncoupling, and not down-regulation, of cardiac adrenoreceptors, is responsible for the early decrease in heart rate at maximal hypoxic exercise.
authors.affiliation: Department of Neuroanaesthesia, Neuroscience Center, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Lundby
authors.forename: P
authors.initials: P
authors.lastname: Møller
authors.forename: I L
authors.initials: IL
authors.lastname: Kanstrup
authors.forename: N V
authors.initials: NV
authors.lastname: Olsen
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D001794:Blood Pressure; D004837:Epinephrine / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006400:Hematocrit; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood; D010102:Oxygen Inhalation Therapy; D017448:Receptors, Dopamine D2 / Q000502:physiology*
chemical_list: D017448:Receptors, Dopamine D2; D019344:Lactic Acid; D010100:Oxygen; D009638:Norepinephrine; D004837:Epinephrine