Effects of Chronic Hypoxia on a Nonmammalian Vertebrate

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DESCRIPTION (provided by applicant): A number of human health problems stem from dysfunctional cardiovascular and ventilatory control processes which have been altered by chronic and/or intermittent hypoxia. These include SIDS, developmental effects in the fetus and neonate, periodic breathing, hypertension, increased risk for stroke, arrhythmias and the long-term effects of various cardio-pulmonary diseases. Some of the physiological responses of mammals to hypoxia are adaptive for sojourn to high altitudes. However, the consequences of some of the responses lead to pathologies. While there has been significant progress towards understanding the effects of chronic and intermittent hypoxia, the neural mechanisms responsible for many of the changes in cardiovascular and ventilatory control remain elusive. Also, significant changes occur in the effect of chronic hypoxia as a mammal matures from a fetus through neonate to adult. An investigation of animals that have the ability to routinely cope with large chronic and intermittent changes in O2 availability may lead the way to a better understanding of human diseases and perhaps novel treatment strategies. The overall objective of this proposal is to use standard physiological measurements and confocal laser microscopy to investigate changes in central and peripheral neural mechanisms responsible for altering cardiovascular and ventilatory control in response to chronic and intermittent hypoxia in the water-breathing channel catfish (Ictalurus punctatus). This study will fill a critical gap in our knowledge of O2 chemoreception. Strategic repetitions of some mammalian studies will allow a the beginning of a comparative/phylogenetic analysis of O2 chemoreception in vertebrates. Other experiments utilizing this novel animal model and the determination of central and peripheral neurotransmitter identities and levels may provide insight into the evolution of O2 chemoreception.