title: Coronary vascular smooth muscle function in E. coli endotoxemia in dogs.
abstract: The purpose of this study was to determine whether intrinsic contraction-relaxation properties of coronary arteries are altered during acute gram-negative endotoxemia. Coronary vascular smooth muscle (VSM) was evaluated in vitro using large and small left circumflex coronary ring preparations isolated from dogs 4 h after administration of either saline (control; C) or 1.5 mg/kg Escherichia coli endotoxin (ET). ET dogs exhibited marked systemic hypotension and cardiovascular depression throughout the 4-h in vivo phase of the study accompanied by reduction in total left ventricular myocardial blood flow. Isolated coronary vessels were stretched to the apex of the length-contractile tension curve; no differences were observed in length-active or length-passive tension (vessel compliance) relationships between C and ET vessels. Isometric contractions produced by K+ and prostaglandin F2 alpha (PGF2 alpha) were similar in C and ET coronary arteries. VSM relaxant responses to nitroprusside (NP; 10(-10) to 10(-4) M) were also similar in C and ET vessels. In contrast to the apparent lack of effect of ET on directly acting VSM agents, relaxation responses to the endothelial-dependent vasodilator acetylcholine (ACh) were significantly less in ET vessels. Impaired vasodilator response to ACh was not improved by in vivo treatment with the combination antioxidant therapy of allopurinol, superoxide dismutase, and catalase. We conclude that both depolarization (K+) and receptor (PGF2 alpha)-mediated contractile mechanisms, as well as basal cGMP (NP)-mediated vasodilator mechanisms, remained functional in coronary vasculature during acute endotoxemia. Inhibition of ACh-mediated relaxation in ET vessels suggests altered endothelial-dependent vasodilation in coronary arteries during endotoxemia, but this change did not seem to be associated causally with oxygen free radicals.
authors.affiliation: John M. Dalton Research Center, University of Missouri, Columbia 65211.
authors.forename: J L
authors.initials: JL
authors.lastname: Parker
authors.forename: R S
authors.initials: RS
authors.lastname: Keller
authors.forename: D V
authors.initials: DV
authors.lastname: DeFily
authors.forename: M H
authors.initials: MH
authors.lastname: Laughlin
authors.forename: M J
authors.initials: MJ
authors.lastname: Novotny
authors.forename: H R
authors.initials: HR
authors.lastname: Adams
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D016166:Free Radical Scavengers; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D004731:Endotoxins; D016166:Free Radical Scavengers; D009599:Nitroprusside; D011189:Potassium Chloride; D015237:Dinoprost; D000109:Acetylcholine