Role of endothelium-derived relaxing factor on vascular reactivity in endotoxin-induced shock

Role of endothelium-derived relaxing factor on vascular reactivity in endotoxin-induced shock. Chinese J. Physiol. The present study showed that E. coli lipopolysaccharide (LPS; 5 mg/kg, i.v.) produced a maximal and significant reduction in mean arterial blood pressure in the anesthetized rat. Pretreatment with N omega-nitro-L-arginine (50 mg/kg, i.v.) produced an increase in mean arterial blood pressure and completely abolished the LPS-induced hypotension. In vitro, it was designed to analyse the mechanisms underlying the LPS-induced hypotension by using various contractile and relaxant agents. Phenylephrine and high-K(+)-induced contraction was less in mesenteric arterial rings from LPS-treated rats than in rings from control rats. The removal of endothelium significantly enhanced the contraction induced by phenylephrine and high-K+ in LPS-treated rats, whereas in control rats, only the contraction induced by phenylephrine was enhanced. In contrast, the relaxation elicited by acetylcholine, A23187, L-arginine and nitroglycerin was greater in mesenteric arterial rings from LPS-treated rats than those from control rats. However, the greater relaxation induced by acetylcholine in LPS-treated rats was completely abolished by N omega-nitro-L-arginine or methylene blue. Additionally, the acetylcholine-induced relaxation was absent by removal of the endothelium. These results suggest that LPS treatment induces the production of nitric oxide from vascular endothelial cells and/or smooth muscle cells then impair the contractile response to vasoconstrictors and enhance the relaxation to vasodilators in small mesenteric arteries.