EFFECT OF BACTERIAL LIPOPOLYSACCHARIDE ON FUNCTION OF RAT SMALL FEMORAL ARTERIES

The effects of endotoxin on endothelial and smooth muscle function wer e investigated in small femoral arteries removed from rats 4 h after i ntraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 20 mg/kg) or solvent. In the absence of L-arginine in the organ bath, the sensitivity of the arteries to norepinephrine (NE) was decreased o nly slightly, and the relaxing effects of neither 3-morpholinosydonimi ne-N-ethyl-carbamide (SIN-1), a nitric oxide (NO) donor, nor acetylcho line (ACh) were modified by LPS treatment despite morphological damage to the endothelium seen with scanning electron microscopy. However, L -arginine (30 mu M to 1 mM), which had no effect on control vessels, c aused a rapid and stereospecific relaxation of arteries from LPS-treat ed rats that was abolished by both N-G-nitro-L-arginine methyl ester ( 1 mM), a NO synthase inhibitor, and methylene blue, an inhibitor of th e activation of guanylyl cyclase by NO. The relaxing effect of L-argin ine was observed in the absence of endothelium, although it was signif icantly greater in its presence. In addition, a 30-min exposure to ext racellular L-arginine (100 mu M) moderately but significantly decrease d the sensitivity to ACh and SIN-1 of vessels from LPS-treated but not from control rats. These results indicate that LPS treatment induced a NO synthase activity in smooth muscle cells of rat small femoral art eries and that the resulting relaxation was dependent on extracellular L-arginine in these resistance vessels. In the presence of a physiolo gical concentration of L-arginine, some decrease in sensitivity to the relaxing effect of NO and ACh occurred in arteries exposed to LPS, pr obably as a consequence of continuous NO production by the LPS-induced NO synthase.