Release of EDRF and NO in ex vivo perfused aorta: inhibition by in vivo E. coli endotoxemia.
Previous studies have yielded contradictory results about interrelations between endotoxin and endothelium-derived relaxing factor (EDRF). We tested the hypothesis that in vivo endotoxemia inhibits basal and/or agonist-mediated release of EDRF and nitric oxide (NO). EDRF bioactivity, NO production, and NO synthase (NOS) activity were measured in aorta from guinea pigs following 16 h of Escherichia coli endotoxemia (4 mg/kg endotoxin i.p.). Endothelium-dependent relaxation of aortic rings was studied under standard isometric conditions. Endotoxemia resulted in an 89% reduction in basal EDRF bioactivity and a 62% reduction in basal NO production in perfused aorta. EDRF bioactivity and NO production in response to the receptor-dependent agonists acetylcholine and ADP were significantly reduced in perfused aorta from endotoxemic animals. In contrast, endotoxin did not significantly inhibit EDRF bioactivity and NO production by the receptor-independent agonist A-23187. Aortic rings from endotoxemic animals likewise showed decreased vasodilator responses to acetylcholine and ADP but not to A-23187. Inducible (Ca2+ independent) NOS activity was not significantly different in control and endotoxin-treated animals. These findings indicate that prolonged endotoxemia resulted in diminution of release of EDRF, consistent with the interpretation that endotoxemia decreases basal and agonist-stimulated EDRF bioactivity and NO production with loss of endothelium-dependent vasodilator reserves during gram-negative sepsis.
Myers
P R
PR
Department of Medicine, Dalton Cardiovascular Research Center, College of Veterinary Medicine, University of Missouri.
Zhong
Q
Q
Jones
J J
JJ
Tanner
M A
MA
Adams
H R
HR
Parker
J L
JL
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity; D004926:Escherichia coli; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010477:Perfusion; D014115:Toxemia / Q000209:etiology / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004731:Endotoxins; D009569:Nitric Oxide; D000001:Calcimycin; D000244:Adenosine Diphosphate; C044101:endotoxin, Escherichia coli; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine