Neurotransmitters and biphasic respiratory response to hypoxia.
Recent work from this laboratory (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 55:483-488, 1983) has shown that the biphasic respiratory response to hypoxia in piglets is due to changing central neural respiratory output. To test the hypothesis that either adenosine or opiatelike neurotransmitters mediate the failure to sustain hyperpnea in response to hypoxia, 12 piglets were studied at a mean age of 2.9 +/- 0.4 days (range 2-6 days). Animals were anesthetized, paralyzed, and ventilated using a servo-controlled system that maintained end-tidal CO2 constant. Electrical activity of the phrenic nerve was recorded as the index of breathing. An initial experimental trial of 6 min ventilation with 15% O2 was performed in all 12 piglets. Thereafter all 12 piglets were treated with aminophylline (n = 6), naloxone (n = 3), or naltrexone (n = 3) and again subjected to 15% O2. During initial exposure to hypoxia there was an initial increase in phrenic activity that was not sustained. During recovery ventilation with 100% O2, phrenic activity transiently declined below the base-line level and then gradually returned. Subsequent intravenous administration of aminophylline, naloxone, or naltrexone caused base-line phrenic activity to increase. Thereafter repeat exposures to 15% O2 were carried out. During these posttreatment trials of hypoxia, phrenic activity further increased, but the hyperventilation was again not sustained. These findings suggest it is unlikely that either adenosine or mu-endorphin neurotransmitters are the primary mediators of the biphasic response to hypoxia in newborns.
D000241:Adenosine / Q000502:physiology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004723:Endorphins / Q000502:physiology; D006985:Hyperventilation / Q000209:etiology; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000503:physiopathology; D012119:Respiration; D013552:Swine
D004723:Endorphins; D018377:Neurotransmitter Agents; D000628:Aminophylline; D009270:Naloxone; D009271:Naltrexone; D000241:Adenosine