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Maintenance of gasping and restoration of eupnea after hypoxia is impaired following blockers of ₁-adrenergic receptors and serotonin 5-HT₂ receptors

Department of Physiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

Submitted 5 June 2007 ; accepted in final form 24 December 2007

In severe hypoxia or ischemia, normal eupneic breathing fails and is replaced by gasping. Gasping serves as part of a process of autoresuscitation by which eupnea is reestablished. Medullary neurons, having a burster, pacemaker discharge, underlie gasping. Conductance through persistent sodium channels is essential for the burster discharge. This conductance is modulated by norepinephrine, acting on ₁-adrenergic receptors, and serotonin, acting on 5-HT₂ receptors. We hypothesized that blockers of 5-HT₂ receptors and ₁-adrenergic receptors would alter autoresuscitation. The in situ perfused preparation of the juvenile rat was used. Integrated phrenic discharge was switched from an incrementing pattern, akin to eupnea, to the decrementing pattern comparable to gasping in hypoxic hypercapnia. With a restoration of hyperoxic normocapnia, rhythmic, incrementing phrenic discharge returned within 10 s in most preparations. Following addition of blockers of ₁-adrenergic receptors (WB-4101, 0.0625–0.500 µM) and/or blockers of 5-HT₂ (ketanserin, 1.25–10 µM) or multiple 5-HT receptors (methysergide, 3.0–10 µM) to the perfusate, incrementing phrenic discharge continued. Fictive gasping was still induced, although it ceased after significantly fewer decrementing bursts than in preparations than received no blockers. Moreover, the time for recovery of rhythmic activity was significantly prolonged. This prolongation was in excess of 100 s in all preparations that received both WB-4101 (above 0.125 µM) and methysergide (above 2.5 µM). We conclude that activation of adrenergic and 5-HT₂ receptors is important to sustain gasping and to restore rhythmic respiratory activity after hypoxia-induced depression.

control of breathing; sudden infant death syndrome

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