Effects of haloperidol and domperidone on ventilatory roll off during sustained hypoxia in cats.
In a previous work, we showed that the adult cat demonstrates a ventilatory decline during sustained hypoxia (the "roll off" phenomenon) and that the mechanism responsible for this secondary decrease in ventilation lies within the central nervous system (J. Appl. Physiol. 63: 1658-1664, 1987). In this study, we sought to determine whether central dopaminergic mechanisms could have a role in the roll off. We studied the effects of haloperidol, a peripheral and centrally acting dopamine receptor antagonist, on the ventilatory response to sustained isocapnic hypoxia (end-tidal PO2 40-50 Torr, 20-25 min) in awake cats. In vehicle control cats (n = 5), sustained hypoxia elicited a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a 24 +/- 6% (P less than 0.01) reduction. In contrast, in haloperidol- (0.1 mg/kg) treated cats (n = 5) the ventilatory roll off was virtually abolished (-1 +/- 1%; P = NS). We also measured ventilatory, carotid sinus nerve (CSN) and phrenic nerve (PhN) responses to sustained isocapnic hypoxia in anesthetized animals (n = 6) to explore the influence of haloperidol on peripheral and central response during the roll off. Control responses to hypoxia showed an initial increase in ventilation, PhN, and CSN activity, followed by a subsequent decline in ventilation and PhN activity of 17 +/- 3 and 17 +/- 5%, respectively (P less than 0.05). In contrast, CSN activity remained unchanged during the roll off. Administration of haloperidol (1 mg/kg) reduced the initial increment in ventilation, while the initial increase in CSN activity was augmented.(ABSTRACT TRUNCATED AT 250 WORDS)
Tatsumi
K
K
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Pickett
C K
CK
Weil
J V
JV
D000818:Animals; D002346:Carotid Sinus / Q000294:innervation; D002415:Cats; D004294:Domperidone / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004594:Electrophysiology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010791:Phrenic Nerve / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D004294:Domperidone; D006220:Haloperidol