[Loss of contractile stability induced by phenylephrine and endothelin in the aorta of rats treated with endotoxin].
The alterations of vascular reactivity in endotoxemia were investigated using the aorta from intraperitoneally endotoxin-injected rats (E. Coli 0111: B4; 10 mg/kg). After 3 hours, rings were removed and isometric contractions recorded. Using single maximal agonist concentration, similar contractions were observed in sham and shocked preparations for phenylephrine (PE), endothelin (ET-1) and phorbol 12, 13 dibutyrate (PDB) but not for KCl. Nevertheless, contraction elicited by PE lost tonicity (105 min observation). This fact was not due to endothelium, prostaglandins (since indomethacin and aspirin were ineffective) PE degradation (since medium contained, propranolol, hydrocortisone acetate, cocaine and EDTA) or excitation-contraction coupling fading (since contraction was restored by other agonists) but may involve synthesis of protein (since cycloheximide significantly antagonized this phenomenon). This loss of tonicity was also observed with ET-1 but was less pronounced with KCl and PDB. In conclusion, endotoxin induced impairment of vascular reactivity may occur through different pathways: contractile events (e.g. calcium influx as exemplified by KCl) and receptor events (loss of tonicity and/or desensitization as exemplified by PE and ET-1) from the different agonists tested, PDB, which activates the protein kinase C, was the less affected by endotoxin.
Auguet
M
M
Institut Henri Beaufour Research Labs, Les Ulis, France.
Delaflotte
S
S
Chabrier
P E
PE
Braquet
P
P
D000818:Animals; D001013:Aorta, Thoracic; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D004731:Endotoxins / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology
D016232:Endothelins; D004731:Endotoxins; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride
Perte de stabilité de la contraction provoquée par la phényléphrine et l'endothéline sur l'aorte de rats traités par l'endotoxine.