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Peripheral chemosensitivity in mutant mice deficient in nitric oxide synthase
1Department of Physiology and Biophysics, Schoool of Medicine, Case Western Reserve University, Cleveland OH 44106, USA.
Advances in Experimental Medicine and Biology
|June 13, 2000
Summary
Nitric oxide (NO) generated by neuronal (NOS-1) and endothelial (NOS-3) enzymes differentially regulate carotid body responses. NOS-1 enhances, while NOS-3 dampens, respiratory reflexes to hypoxia and chemical stimuli.
Area of Science:
- Physiology
- Neuroscience
- Respiratory Regulation
Background:
- Nitric oxide (NO) is endogenously produced by neuronal (NOS-1) and endothelial (NOS-3) isoforms.
- Both NOS isoforms are present in the carotid body, a key chemosensory organ.
- Endogenous NO is known to modulate carotid body activity.
Purpose of the Study:
- To investigate the distinct roles of NOS-1 and NOS-3 in mediating respiratory reflexes originating from the carotid body.
- To determine the relative contributions of each NOS isoform to chemosensory responses.
Main Methods:
- Experiments utilized mutant mice lacking either NOS-1 or NOS-3, alongside wild-type controls.
- Respiration was assessed in conscious mice using plethysmography.
- Phrenic nerve activity was monitored in anesthetized mice as an index of breathing.
- Responses to hypoxia, cyanide, and hyperoxia were evaluated.
Main Results:
- NOS-1 deficient mice showed augmented ventilatory responses to hypoxia and cyanide compared to wild-type.
- NOS-3 deficient mice exhibited blunted respiratory responses to hypoxia and cyanide.
- Respiratory depression during hyperoxia was more pronounced in NOS-1 mutants and nearly absent in NOS-3 mutants.
Conclusions:
- NO derived from NOS-1 enhances carotid body-mediated respiratory reflexes.
- NO derived from NOS-3 attenuates carotid body-mediated respiratory reflexes.
- Neuronal and endothelial NOS isoforms exert opposing modulatory effects on carotid body chemosensitivity.