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MODEL ORGANISMS AND COMPARATIVE FUNCTIONAL GENOMICS
1Department of Physiology, Showa University School of Medicine, Tokyo 142-8555; 2Department of Molecular Genetics, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015; and 3Department of Internal Medicine II, Nara Medical University, Kashihara 634-8522, Japan
Submitted 3 March 2003 ; accepted in final form 21 June 2003
The purpose of this study was to test whether chronically enhanced
O2 delivery to tissues, without arterial hyperoxia, can change
acute ventilatory responses to hypercapnia and hypoxia. The effects of
decreased hemoglobin (Hb)-O2 affinity on ventilatory responses
during hypercapnia (0, 5, 7, and 9% CO2 in O2) and
hypoxia (10 and 15% O2 in N2) were assessed in mutant
mice expressing Hb Presbyterian (mutation in the
-globin gene,
108
Asn
Lys). O2 consumption during normoxia, measured via
open-circuit methods, was significantly higher in the mutant mice than in
wild-type mice. Respiratory measurements were conducted with a whole body,
unrestrained, single-chamber plethysmograph under conscious conditions. During
hypercapnia, there was no difference between the slopes of the hypercapnic
ventilatory responses, whereas minute ventilation at the same levels of
arterial PCO2 was lower in the Presbyterian mice than in
the wild-type mice. During both hypoxic exposures, ventilatory responses were
blunted in the mutant mice compared with responses in the wild-type mice. The
effects of brief hyperoxia exposure (100% O2) after 10% hypoxia on
ventilation were examined in anesthetized, spontaneously breathing mice with a
double-chamber plethysmograph. No significant difference was found in
ventilatory responses to brief hypoxia between both groups of mice, indicating
possible involvement of central mechanisms in blunted ventilatory responses to
hypoxia in Presbyterian mice. We conclude that chronically enhanced
O2 delivery to peripheral tissues can reduce ventilation during
acute hypercapnic and hypoxic exposures.
hyperoxia; hypoxia; hypercapnia; tissue; breathing
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