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The most logical explanation for all these results is that TNF stimulates the endothelium to synthesize surface proteins (eg, ELAM) that interfere with either the synthesis or release of EDRF. This type of response may be important in situations in which TNF is released into the blood, such as endotoxin shock. It also occurs in the absence of white blood cells (lymphocytes, monocytes, macrophages, neutrophils), which are the major source of cytokines like TNF, since epithelial and endothelial cells can also produce these cytokines (eg, TNF, interleukin-1) which have similar biologic effects. One implication of this inhibition of vasorelaxation is interference with compensatory vasodilation in situations such as circulatory shock due to a prolonged deficit in nutritive blood flow to vital tissues. Another possible consequence of this TNF effect could be to tilt vascular control mechanisms in favor of prolonged vasoconstriction or even vasospasm due to the loss of vasodilator reserve mechanisms. This could be important in triggering transient ischemic attacks in the cerebral circulation or coronary vasospasm in the myocardial vasculature. The coronary vasospasm could also contribute to the pathogenesis of myocardial ischemia.