Modulation of hypoxic ventilatory response by systemic platelet-activating factor receptor antagonist in the rat

N. Simakajornboon, G. R. Graff, J. E. Torres, D. Gozal

Research output: Contribution to journalArticle

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Abstract

Platelet activating factor (PAF) has recently emerged as an important modulator of neuronal excitability by enhancing synaptic glutamate release. Since PAF receptors (PAFR) are ubiquitously distributed in the brain, we hypothesized that PAF may play a role in respiratory control. To examine this issue, hypoxic (10% O2 for 15 min, n=14) and hypercapnic (5% CO2 for 30 min, n=6) challenges were performed in chronically-instrumented, unrestrained adult rats following administration of the pre-synaptic PAFR antagonist BN52021 (i.p. 20 mg/kg in 0.5 ml) or vehicle (Veh). In normoxia, BN52021 elicited Vt decreases and corresponding f increases such that minute ventilation (Ve) was unaffected. During hypercapnia, peak Ve increased similarly after both treatments (103±18% in BN52021 vs. 94±19% in Veh, p-NS). In contrast, significant reductions in the peak hypoxic Ve response occurred after BN52021 (42±10% vs. 104±18% in Veh, P<0.002). BN52021 increased normoxic arterial blood pressure and decreased heart rate. However, hypoxia-induced chronotropic responses were attenuated and depressor responses were enhanced by BN52021. We further examined protein kinase C (PKC) translocation patterns during acute hypoxia after systemic BN52021 administration. Activation of PKC β and δ was blocked by BN52021, PKC γ was attenuated, with no effects on PKC α, ε, θ, ι, μ, and ζ. We conclude that systemic administration of a PAFR antagonist attenuates cardioventilatory recruitment to hypoxia and selectively attenuates activation of PKC in the rat brainstem. We speculate that enhanced regional PAF production and release during hypoxic conditions may contribute important excitatory inputs and signal transduction pathways within neuronal structures underlying cardiovascular and respiratory control. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)213-225
Number of pages13
JournalRespiration Physiology
Volume114
Issue number3
DOIs
Publication statusPublished - Dec 1 1998

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine

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