Cardiorespiratory responses to systemic administration of a protein kinase C inhibitor in conscious rats

David Gozal, Gavin Graff, José E. Torres, Sanjay G. Khicha, Gautam S. Nayak, Narong Simakajornboon, Evelyne Gozal

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Although protein kinase C (PKC) is an essential component of multiple neurally mediated events, its role in respiratory control remains undefined. The ventilatory effects of a systemically active PKC inhibitor (Ro-32-0432; 100 mg/kg ip) were assessed by whole body plethysmography during normoxia, hypoxia (10% O2), and hyperoxia (100% O2) in unrestrained Spragne-Dawley rats. A sustained expiratory time increase occurred within 8-10 min of injection in room air [mean 44.8 ± 5.2 (SE) % ], was similar to expiratory time prolongations after Ro-32-0432 administration during 100% O2 (45.5 ± 8.1%; not significant), and was associated with mild minute ventilation (V̇E) decreases. Hypercapnic ventilatory responses (5% CO2) remained unchanged after Ro-32-0432. During 10% O2, V̇E increased from 122.6 ± 15.6 to 195.7 ± 10.1 ml/min in vehicle-treated rats (P < 0.001). In contrast, marked attenuation of V̇E hypoxic responses occurred after Ro-32-0432 [86.2 ± 6.2 ml/min in room air to 104.1 ± 7.1 ml/min in 10% O2; pre- vs. post- Ro-32-0432, P < 0.001 (analysis of variance)]. Overall, PKC activity was reduced and increases with hypoxia were abolished in the particulate subcellular fraction of brain tissue after Ro-32-0432 treatment, indicating that this compound readily crosses the blood-brain barrier. We conclude that systemic PKC inhibition elicits significant centrally mediated expiratory prolongations and ventilatory reductions as well as blunted ventilatory responses to hypoxia but not to hypercapnia. We postulate that PKC plays an important role in signal transduction pathways within brain regions underlying respiratory control.

Original languageEnglish (US)
Pages (from-to)641-648
Number of pages8
JournalJournal of applied physiology
Volume84
Issue number2
DOIs
StatePublished - Feb 1998

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

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