title: Endotoxin impairs endothelium-dependent vasodilation more in the coronary and renal arteries than in other arteries of the rat.
abstract: Endotoxemia may result in endothelial dysfunction, and some vascular beds may be affected more than others. To test this hypothesis, we studied, in vitro, the reactivity of isolated rat coronary, renal, superior mesenteric, and hepatic arteries exposed to endotoxin (E. coli, 50 microg. mL(-1)) or saline for 2 h at 37 degrees C. Vascular smooth muscle function was tested using 125 mM KCl, the vasoconstrictors norepinephrine (NE), and the thromboxane analog U46619 (coronary artery). Endothelium-dependent vasorelaxation was tested with acetylcholine (ACh) in preconstricted vessels. Although differing between vessel types, the smooth muscle contractile responses were not affected by endotoxin, either in the presence or absence of L-arginine. Endotoxin impaired the response to ACh in rat coronary arteries (92.7 +/- 4.6% vasodilation in control and 41.3 +/- 11.6% in endotoxin-exposed segments) and in renal arteries (66.7 +/- 5.2% vasodilation in control and 43.2 +/- 4.9% in endotoxin-exposed segments), so that there was a mean 55% decrease vs controls in coronary and a mean 35% decrease in renal arteries. Endotoxin did not affect superior mesenteric and hepatic arteries. Brief endotoxin exposure of isolated rat arteries may thus inactivate endothelial NO synthase, independent of iNOS. The increase in heterogeneity among endothelium-dependent vasodilation after endotoxin may help to explain early blood flow maldistribution in endotoxin shock.
authors.affiliation: Laboratorium for Physiology, Medical Intensive Care Unit, Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Harro A
authors.initials: HA
authors.lastname: Piepot
authors.forename: A B Johan
authors.initials: AB
authors.lastname: Groeneveld
authors.forename: Antonie A
authors.initials: AA
authors.lastname: van Lambalgen
authors.forename: Pieter
authors.initials: P
authors.lastname: Sipkema
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D006499:Hepatic Artery / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects*; D012772:Shock, Septic / Q000276:immunology / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004731:Endotoxins; D017382:Reactive Oxygen Species; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat