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HIF‐1a gene deletion in the nucleus tractus solitarii (NTS) blunts ventilatory acclimatization to hypoxia (VAH)
Author(s) -
Go Ariel D.,
Fu Zhenxing,
Johnson Randall S.,
Powell Frank L.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.704.15
Subject(s) - microinjection , carotid body , hypoxia (environmental) , cre recombinase , ventilation (architecture) , microbiology and biotechnology , chemistry , endocrinology , medicine , biology , gene , transgene , genetically modified mouse , electrophysiology , biochemistry , oxygen , organic chemistry , mechanical engineering , engineering
Previously, we found that Hypoxia‐Inducible Factor‐1α (HIF‐1α) expression in the central nervous system (CNS) is necessary for normal VAH in mice. Here we tested the hypothesis that HIF‐1α in the NTS, which receives sensory input from carotid body chemoreceptors, is necessary during hypoxic exposure for normal VAH. We used the Cre‐LoxP strategy and microinjected Adeno‐associated virus expressing Cre‐recombinase (AAV‐Cre) into the NTS of mice carrying conditional HIF‐1α floxed alleles. AAV‐LacZ was microinjected as a control and to determine the extent of AAV expression. One week after microinjection, mice were kept in normoxia (CN) or CH (P io 2 = 70 Torr) for 7 days before measuring the hypoxic ventilatory response with barometric pressure plethysmography. Ventilation (V i mL/(min kg)) was:CHRONIC NORMOXIA Inspired O 2 (%) AAV‐Cre (n=6) AAV‐LacZ (n=6)21 2176 ± 158 2059 ± 106 10 2088 ± 181 1905 ± 84CHRONIC HYPOXIAInspired O 2 (%) AAV‐Cre (n=9) AAV‐LacZ (n=8)21 2811 ± 121 2949 ± 152 10 3092 ± 245 4566 ± 307CH significantly increased V i as expected, but the increases in V i and breathing frequency in CH were significantly less with AAV‐Cre than with AAV‐LacZ. The results support HIF‐1α in the NTS contributing to the increased CNS gain of the HVR in VAH we reported previously ( J. Appl. Physiol. 87: 817–823, 1999). Supported by NIH RO1 HL‐081823 and 1P01 HL 098053.