Platelet-activating factor receptor and respiratory and metabolic responses to hypoxia and hypercapnia.
Activation of the platelet-activating factor receptor (PAFR) regulates neural transmission. A PAFR blocker reduced the peak hypoxic (pHVR) but not hypercapnic ventilatory (HCVR) responses in rats [Am. J. Physiol. 275 (1998) R604]. To further examine the role of PAFR in respiratory control, genotype-verified PAFR -/- and PAFR +/+ adult male mice underwent hypoxic and hypercapnic challenges. HCVR was similar in the two groups (p-NS). However, pHVR was significantly reduced in PAFR -/- mice (38 +/- 13% baseline [S.D.]) compared to PAFR +/+ mice (78 +/- 16% baseline; P < 0.001, ANOVA), with reduced tidal volume recruitments during pHVR. In addition, hypoxic ventilatory depression was attenuated in PAFR -/- mice (P < 0.01), and was primarily due to attenuation of the time-dependent decreases in oxygen consumption during sustained hypoxia (P < 0.01). Thus, PAFR expression/function modulates components of the acute ventilatory and metabolic adaptations to hypoxia but not to hypercapnia. Imbalances in PAFR activity may lead to maladaptive regulation of the tightly controlled metabolic-ventilatory relationships during hypoxia.
Reeves
Stephen R
SR
Departments of Pediatrics and Pharmacology and Toxicology, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Suite 204, 570 South Preston St., Louisville, KY 40202, USA.
Gozal
David
D
D000222:Adaptation, Physiological; D000818:Animals; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010101:Oxygen Consumption / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D012123:Pulmonary Ventilation / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology*
D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor