Regulation of Neuronal Nitric Oxide Synthase Gene Expression by Hypoxia

Abstract

Nitric oxide synthase (NOS) catalyzes the formation of nitric oxide (NO) in mammalian cells. Three isoforms of NOS have been isolated that include inducible (i), endothelial (e) and neuronal (n) NOS. We have previously reported the distribution of nNOS in carotid bodies as well as in brain stem neurons that process peripheral chemoreceptor inputs (Prabhakar et al 1993, 1995a). Physiological studies have further shown that endogenous NO modulates the ventilatory response to hypoxia by acting both at peripheral chemoreceptors and central neurons. Chronic hypoxia is known to trigger expression of several genes including erythropoietin (Goldberg et al, 1988); tyrosine hydroxylase (Czyzyk-Krzeska et al, 1994), c-fos protoncogene (Prabhakar et al, 1995b). The objective of the present study is to examine whether chronic hypoxia also regulates nNOS gene expression, and if so to assess the role of NO in ventilatory adaptations to hypoxia.