Cyclic nucleotide regulation of interleukin-1β induced nitric oxide synthase expression in vascular smooth muscle cells

Experiments were performed to examine the effect of cyclic nucleotides on the expression of inducible nitric oxide synthase (iNOS) activity by interleukin-1 beta (IL- 1 beta) treated rat aortic smooth muscle cells (SMC). Treatment of vascular SMC with IL-1 beta stimulated iNOS mRNA expression and the subsequent release of nitrite, a stable oxidation product of nitric oxide (NO). Similarily, lipophilic analogues of cAMP also induced both iNOS mRNA expression and nitrite release. The addition of IL-1 beta and cAMP derivatives resulted in a synergystic enhancement of both iNOS mRNA production and of nitrite formation. In contrast, Lipophilic analogues of cGMP did not induce iNOS expression. The addition of cGMP derivatives modestly increased IL-1 beta-induced SMC nitrite generation without affecting the production of iNOS mRNA. The capacity of cyclic nucleotides to positively modulate the induction of iNOS activity may play an important role in regulating the release of NO in vivo.