Contractile elements in the regulation of macromolecular permeability

The leakage of macromolecules from the vasculature to the interstitium is greatly accentuated by mediators of edema such as histamine and bradykinin. The mechanism for this effect is not well delineated although many agents that affect smooth muscle tone may also affect macromolecular leakage. Leakage occurs primarily from the small venules. The demonstration that mediators of edema produce interendothelial gaps in the venules as well as changes in the shape of the endothelial nuclei has led to the hypothesis that a contraction of a vascular wall component may be responsible for the observed leakage of macromolecules. This component does not appear to be the vascular smooth muscle itself. Two other elements of the vascular wall, the endothelium and the pericytes, have been shown to contain many of the same elements of the contractile machinery present in smooth muscle. Most recent studies have presumed that endothelial cell contraction is responsible for the formation of the interendothelial gaps through which the macromolecules move. However, endothelial contraction has been difficult to demonstrate experimentally. Alternatively, inasmuch as pericytic processes can end near endothelial junctions and there is an abundance of fibronectin between the pericytes and the endothelium, it may be a pericytic contraction that causes the interendothelial gap formation.