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.
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
M H
MH
Yen
S J
SJ
Chen
C C
CC
Wu
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine