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1 Department of Physiology, Dartmouth Hitchcock Medical Center, Dartmouth College, Lebanon, New Hampshire 03756; and 2 Department of Medical Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada T2N 4N1
Nitric oxide (NO) is a potent central neuromodulator of respiration, yet its scope and site of action are unclear. We used 7-nitroindazole (7-NI), a selective inhibitor of endogenous neuronal NO synthesis, to investigate the neurogenesis of respiration in larval bullfrog (Rana catesbeiana) isolated brain stems. 7-NI treatment (0.0625-0.75 mM) increased the specific frequency of buccal ventilation (BV) events, indicating influence on BV central rhythm generators (CRGs). The drug reduced occurrence, altered burst shape, and disrupted clustering of lung ventilation (LV) events, without altering their specific frequency. LV burst occurrence and clustering also differed between pH conditions. We conclude that NO has diverse effects on respiratory rhythmogenesis, being necessary for the expression of respiratory rhythms, inhibiting the frequency of BV CRG, and affecting both shape and clustering of LV bursts through conditional modulation of LV CRG. We confirm central chemosensitivity in these preparations and demonstrate chemomodulation of LV burst clustering and occurrence but not specific frequency. Results support distinct oscillators underlying LV and BV CRGs.
nitric oxide synthase; neuronal nitric oxide synthase; nitric oxide synthase-1; breathing; central pattern generation; central chemoreception; carbon dioxide; 7-nitroindazole; L-arginine; amphibian; tadpole; Rana catesbeiana; episodic periodic discontinuous clustered breathing
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