NITRIC-OXIDE RELEASE FROM RAT AORTIC SMOOTH-MUSCLE CELLS IS NOT ATTENUATED BY ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS

We investigated the effects of angiotensin converting enzyme inhibitors on nitric oxide (NO) synthesis in cultured rat vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of NO, and the expression of inducible NO synthase mRNA by vascular smooth muscle cells. Incubation of the culture with interleukin-1 beta (10 ng/ml) for 24 h caused a significant increase in nitrite levels. The basal and interleukin-1 beta-induced nitrite production by vascular smooth muscle cells were not affected by the presence of angiotensin converting enzyme inhibitors (0.1 similar to 10 mu M), enalaprilat, cilazaprilat or captopril. Unstimulated vascular smooth muscle cells expressed no inducible NO synthase transcripts, whereas incubation with interleukin-1 beta 4 h induced marked inducible NO synthase mRNA expression. The angiotensin converting enzyme inhibitors, however, had no effects on the interleukin-1 beta-induced inducible NO synthase mRNA expression. These results indicate that angiotensin converting enzyme inhibitors do not attenuate NO synthesis by vascular smooth muscle cells under basal and interleukin-1 beta-stimulated conditions.