Submitted on February 24, 2004
Accepted on April 14, 2004
Platelet-Activating Factor Receptor Modulates Respiratory Adaptation to Long-Term Intermittent Hypoxia in Mice
Stephen R Reeves1 and David Gozal1*
1 Departments of Pediatrics and Pharmacology & Toxicology, University of Louisville School of Medicine, Kosair Children's Hospital Research Institute, Louisville, KY, USA
* To whom correspondence should be addressed. E-mail: david.gozal{at}louisville.edu.
During hypoxia, release of Platelet-Activating Factor (PAF) and activation of its cognate receptor (PAFR) regulates neural transmission and is required for full expression of peak hypoxic ventilatory response (pHVR) but not hypercapnic ventilatory response. However, it is unclear whether PAFR underlie components of long-term ventilatory adaptations to hypoxia. To examine this issues, adult male PAFR +/+ and PAFR -/- mice were exposed to intermittent hypoxia (IH) consisting of 90 sec 21% O2 and 90 sec 10 % O2 for 30 days, and normoxic and hypoxic ventilatory patterns were assessed using whole-body plethysmography. Starting at day 14 of IH, normoxic ventilation in PAFR -/- was significantly reduced compared to PAFR +/+ mice (p<0.001), the latter exhibiting a prominent long-term ventilatory facilitation (LTVF). However, IH-exposed PAFR -/- mice had markedly enhanced pHVR and hypoxic ventilatory decline (HVD) which became similar to those of IH-exposed PAFR +/+ mice (p-NS). Thus, we postulate that PAFR expression and/or function underlies critical components of IH-induced LTVF but does not play a role in the potentiation of HVR following IH exposures.
