title: Endotoxin induces metabolic dysregulation of vascular tone.
abstract: The goals of this study were to determine 1) if endotoxin alters vascular responsiveness to metabolic stimuli and 2) if the decompensatory loss of skeletal muscle vascular tone that occurs during endotoxemia is induced by increased muscle metabolism. Vascularly isolated and denervated canine gracilis muscles were perfused in situ at a constant flow. In the first set of experiments, gracilis muscle O2 extraction (MVO2) and perfusion pressure were continuously measured during direct electrical stimulation of the muscle mass. Endotoxemia was induced by a 30-min intravenous infusion of Escherichia coli endotoxin (2 mg/kg), and the stimulations were repeated 60 min postendotoxemia. Compared with the nonendotoxic control, the endotoxemic muscle stimulation resulted in a decreased MVO2, and the vascular response (dilation) was potentiated. In the second set of experiments, the MVO2 of the experimental muscle (GMe) was lowered by cooling the temperature of the blood perfusing the muscle to 22-24 degrees C while maintaining the temperature of the contralateral control muscle (GMc) at 34-35 degrees C. After the administration of endotoxin, arterial pressure fell and the GMc showed a progressive increase in MVO2 and loss of vascular tone (decompensation). Coincidently, the GMe showed no significant change in MVO2 and did not vasodilate. The major findings of this study are 1) endotoxin induces the vasculature to become more reactive to metabolic vasodilation, and 2) the decompensatory vasodilation typically observed during endotoxemia can be abolished if MVO2 (i.e., metabolism) is kept low by cooling the muscle. The data suggest that endotoxemia increases vascular sensitivity to vasodilatory metabolites, which allows local mechanisms to dominate extrinsic nonneural forces and control vascular tone, thus inducing vasodilation.
authors.affiliation: Department of Physiology, University of South Carolina School of Medicine, Columbia 29208.
authors.forename: J C
authors.initials: JC
authors.lastname: Hershey
authors.forename: R F
authors.initials: RF
authors.lastname: Bond
mesh_terms: D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006614:Hindlimb; D066298:In Vitro Techniques; D009132:Muscles / Q000098:blood supply / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D014664:Vasodilation; D014666:Vasomotor System / Q000187:drug effects*
chemical_list: D004731:Endotoxins