Recovery of vascular tissue contractile function during sustained endotoxin exposure.
Rat aortic rings incubated in vitro with endotoxin (10 ng/ml, 24 h) exhibited marked suppressions of sensitivity and maximum contraction to norepinephrine as well as a significant increase in guanosine 3',5'-cyclic monophosphate (cGMP) levels. Increasing the incubation time to 42 h did not result in greater suppression; instead, these rings showed improved contractile performance and control-level cGMP. Rings incubated with endotoxin for 18 h and then allowed to recuperate in control medium for another 24 h exhibited normal maximal contractions and cGMP levels; however, these rings remained less sensitive to norepinephrine. An endotoxin-neutralizing protein (50 ng/ml) shielded rings from endotoxin-induced contractile suppression if present during incubation but was unable to restore tissue sensitivity to normal levels if present during the 24-h recuperation. These findings show that vascular tissue exposed to endotoxin has a varied and time-dependent ability to counter the effects of endotoxin on contractile function and intracellular cGMP.
McKenna
T M
TM
Septic Shock Research Program, Naval Medical Research Institute, Bethesda, Maryland 20889.
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006737:Horseshoe Crabs / Q000737:chemistry; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014020:Tissue Extracts / Q000494:pharmacology; D014661:Vasoconstriction
D004731:Endotoxins; D014020:Tissue Extracts; D006152:Cyclic GMP