Vascular endothelium contributes to decreased aortic contractility in experimental sepsis.
In this study, we compared responses to norepinephrine (NE) by thoracic aortic rings isolated from rats made septic by cecal ligation with puncture, and aortic tissue from sham-operated control rats. We also examined the responses of septic and sham-operated rat aortas after removal of the vascular endothelium. Acetylcholine caused relaxation of NE-induced contractions in septic and sham tissue with an intact endothelium but had no effect on tissue with the endothelium removed experimentally. In preparations with intact endothelium, septic tissue manifests a significantly diminished maximal contractile response to NE (424 +/- 62 (SE) mg tension/mg tissue) in comparison to sham tissue (747 + 30). Tissues with the endothelium removed show no significant maximal contractile difference between septic (688 +/- 23) and sham (669 +/- 32) preparations, or the equivalent sham tissue with an intact endothelium. No difference in the log ED50 for sham tissue (-7.33 +/- 0.12 M) and septic tissue (-7.53 +/- 0.15) with intact endothelium existed. Removal of the endothelium from both septic and sham tissue shifted the dose response curves to the left, disclosing a significant difference in the ED50 between sham (-8.88 +/- 0.14) and septic (-8.18 +/- 0.20) tissue. In conclusion, a significant impairment of vascular contractility in response to NE, with no change in ED50, persists in septic vascular tissue in vitro, and the sepsis-induced defect in contractility is mediated, at least in part, by vascular endothelium, since removal of the endothelium partially restores the NE-stimulated contraction to normal.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D002432:Cecum; D004727:Endothelium / Q000502:physiology; D008026:Ligation; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects*
D000109:Acetylcholine; D009638:Norepinephrine