Chronic Administration of the Nitric Oxide Synthase Inhibitor, L-NAME, Increases Circulating Endothelin Levels in Guinea Pigs

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Abstract
Endothelin and nitric oxide are both endothelium-derived vasoactive factors which appear to play a role in a variety of circulatory disorders (Leppaluoto and Ruskoaho, 1992; Moncada et al., 1991; Nathan, 1992; Rubanyi and Parker Botelho, 1991). Boulanger and Lüscher (1990) noted in isolated blood vessels that the release of endothelin and nitric oxide were inversely related. The intracellular levels of cGMP appear to be the determinant of this response, i.e., nitric oxide elevated cGMP and decreased endothelin release, while decreased cGMP promotes endothelin release. In contrast to the inhibition of endothelin release by nitric oxide, Hirata et al. (1993) noted that endothelin promotes nitric oxide release in cultured bovine endothelial cells.