Data supporting the hypothesis that dopamine-2 receptors (D-2-R) contribute to time-dependent changes in the hypoxic ventilatory response (HVR) during acclimatization to hypoxia are briefly reviewed. Previous experiments with transgenic animals (D-2-R 'knockout' mice) support this hypothesis (J. Appl. Physiol. 89 (2000) 1142). However, those experiments could not determine (1) if D-2-R in the carotid body, the CNS, or both were involved, or (2) if D-2-R were necessary during the acclimatization to hypoxia versus some time prior to chronic hypoxia, e.g. during a critical period of development. Additional experiments on C57BL/6J mice support the idea that D-2-R are critical during the period of exposure to hypoxia for normal ventilatory acclimatization. D-2-R in carotid body chemoreceptors predominate under control conditions to inhibit normoxic ventilation, but excitatory effects of D-2-R, presumably in the CNS, predominate after acclimatization to hypoxia. The inhibitory effects of D-2-R in the carotid body are reset to operate primarily under hypoxic conditions in acclimatized rats, thereby optimizing O-2-sensitivity. (C) 2003 Elsevier Science B.V. All rights reserved.
机构:
Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USAColumbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USA
机构:
Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Kolling Inst Med Res,Pain Management Res Inst, Sydney, NSW, AustraliaUniv Sydney, Royal North Shore Hosp, Northern Clin Sch, Kolling Inst Med Res,Pain Management Res Inst, Sydney, NSW, Australia
Winters, Bryony Laura
Vaughan, Christopher Walter
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Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Kolling Inst Med Res,Pain Management Res Inst, Sydney, NSW, AustraliaUniv Sydney, Royal North Shore Hosp, Northern Clin Sch, Kolling Inst Med Res,Pain Management Res Inst, Sydney, NSW, Australia