Effects of antiendothelin treatment on the early hemodynamic changes in hyperdynamic endotoxemia.
We have performed a series of experiments to study the effects of a newly developed antisense homology box-derived endothelin (ET) antagonist peptide (ETR-P1/fl) on the early hemodynamic changes in a hyperdynamic endotoxemic dog model. Mean arterial pressure (MAP), cardiac output (CO) and myocardial contractility (MC) were measured in closed-chest animals. Plasma levels of ET-1,2 were determined by radioimmunassay. A hyperdynamic circulatory response was elicited with a 2-hour infusion of 5.3 micrograms/kg of E. coli endotoxin (ETX). Control and ETX-treated animals received an infusion of ETR-P1/fl (0.1 mg/kg) i.v. ETX treatment decreased MAP and MC, increased initially CO, and a long lasting elevation in the plasma ET level was observed. In ETX-treated animals the administration of ETR-P1/fl significantly prolonged the increase in CO and inhibited the depression of MC. Our results suggest that treatment with the ET antagonist ETR-P1/fl may be advantageous in the early phase of endotoxemia.
Kaszaki
J
J
Institute of Experimental Surgery, Szent-Györgyi Albert Medical University, Szeged, Hungary.
Wolfárd
A
A
Boros
M
M
Baranyi
L
L
Okada
H
H
Nagy
S
S
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D019333:Endothelin-2 / Q000097:blood; D019446:Endotoxemia / Q000188:drug therapy*; D004731:Endotoxins / Q000008:administration & dosage / Q000009:adverse effects; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D009200:Myocardial Contraction / Q000187:drug effects; D010455:Peptides / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
C109027:ETR-p1-f1 antisense peptide; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019333:Endothelin-2; D004731:Endotoxins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides