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.