The effects of tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) were studied in porcine coronary arteries without endothelium. Rings of the artery were incubated in minimum essential medium with TNF-alpha or LPS for 6 or 24 h. After 6 h incubation, the rings were suspended in organ chambers filled with physiological salt solution containing indomethacin for the measurement of isometric force. The rings were contracted with prostaglandin F2 alpha before the addition of L-arginine. In rings treated with TNF-alpha or LPS, L-arginine caused a concentration-dependent relaxation that was abolished by N omega-nitro-L-arginine [an inhibitor of nitric oxide (NO) synthase]. However, contractions to 5-hydroxytryptamine were not affected by TNF-alpha and LPS. After 24 h of incubation, TNF and LPS impaired the contractions to 5-hydroxytryptamine and increased the accumulation of nitrite, a stable degradation product of NO. These effects of TNF-alpha and LPS were blocked by N omega-nitro-L-arginine. Cycloheximide (an inhibitor of protein synthesis) attenuated the inhibitory effect of TNF-alpha and LPS on contractions to 5-hydroxytryptamine. Thus, in the porcine coronary artery without endothelium, TNF-alpha and LPS can induce an L-arginine-NO pathway.