Role of prostaglandin-mediated vasodilatation in inflammation

The mode of action of prostaglandins in inflammation is re-examined by measuring both increased blood flow and plasma exudation and the results presented here suggest that the mediation of vasodilatation and increased vascular permeability should be considered separately.

Abstract

INFLAMMATORY reactions are characterised by hyperaemia, and exudation of plasma resulting in tissue swelling. Putative mediators of inflammation have usually been evaluated according to their ability to mimic inflammatory reactions1. Although prostaglandins were identified in inflammatory exudates2, and prostaglandin synthesis in vitro was shown to be inhibited by nonsteroid anti-inflammatory compounds3–5, prostaglandins (unlike histamine and bradykinin) were found to be poor at eliciting plasma exudation when injected into guinea pig6,7 or rabbit skin8. But, the finding that exogenous prostaglandins (notably of the E-type) potentiate plasma exudation produced by other mediators7–11 suggested that this may be the role of prostaglandins in inflammation. An alternative view has been proposed by Kuehl et al.12, who consider that since E and F prostaglandins fail fully to mimic inflammatory reactions, other products of arachidonic acid should be considered as mediators. They suggest that the unstable prostaglandin endoperoxide, PGG2, or a nonprostaglandin product of it (a free radical could be the important mediator. We have re-examined the mode of action of prostaglandins in inflammation by measuring both increased blood flow and plasma exudation. The results presented here suggest that the mediation of vasodilatation and increased vascular permeability should be considered separately. Prostaglandins (notably the E-type13,14) mediate vasodilatation (although they may have some additional mast cell degranulating activity in the rat15). It is this vasodilatation which is responsible for the potentiation of the exudation produced by other mediators. Our observations provide a new hypothesis for the microvascular mechanisms involved in the action of non-steroid anti-inflammatory compounds.