Effect of nitric oxide gas on the generation of nitric oxide by isolated blood vessels: implications for inhalation therapy.

1. We have investigated, using rat aortic rings, whether exogenous nitric oxide (NO) gas affects the activity or expression of the inducible, Ca(2+)-independent NO synthase. 2. Incubation of rings with lipopolysaccharide (LPS, S. typhosa) for 6 h resulted in a gradual loss of tissue tone, a time-dependent reduction in constrictor response to phenylephrine and significant expression and activity of Ca(2+)-independent NO synthase. 3. Following incubation of LPS-treated rings with NO gas, the expression of inducible NO synthase mRNA was still observed, although the enzyme activity was significantly reduced and there was no reduction in the response to phenylephrine. 4. Therefore, NO gas can inhibit the action but not the induction of an NO synthase likely to play a role in inflammatory states such as adult respiratory distress syndrome (ARDS). 5. These observations may explain the rebound phenomenon observed in some ARDS patients following inhalation therapy with NO gas.