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Am J Physiol Regul Integr Comp Physiol 285: R747-R753, 2003. First published June 26, 2003; doi:10.1152/ajpregu.00104.2003
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MODEL ORGANISMS AND COMPARATIVE FUNCTIONAL GENOMICS

The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with Presbyterian hemoglobinopathy

Masahiko Izumizaki,1 Masakatsu Tamaki,2 Yo-ichi Suzuki,2 Michiko Iwase,1 Takuji Shirasawa,2 Hiroshi Kimura,3 and Ikuo Homma1

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 {beta}-globin gene, {beta}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



Address for reprint requests and other correspondence: I. Homma, Dept. of Physiology, Showa Univ. School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan (E-mail: ihomma{at}med.showa-u.ac.jp).




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