Radioactive colloidal gold as a tool to quantify extravasation of macromolecules in the rat cremaster muscle

Since previously described simple methods were too insensitive to quantify the extent of microvascular permeability increase in the rat cremaster muscle, we applied a new quantitative technique using radioactive colloidal gold (198Au) as the macromolecular tracer. Dose-response effects on microvascular permeability were found with increasing doses of subscrotally injected serotonin or histamine. The presence of colloidal gold particles in the subendothelial space of the postcapillary venules, as verified ultrastructurally, indicated endothelial permeation of the tracer macromolecules. The increased permeability elicited by serotonin was inhibited in a dose-dependent way by serotonin receptor antagonists (potency: methysergide greater than or equal to ketanserin = ritanserin greater than cinanserin), suggesting the presence of functional S2-serotonergic receptors on postcapillary venular endothelial cells. A dose-related inhibition of the histamine-induced extravasation was seen with the H1 antagonists astemizole and azatidine (astemizole greater than azatidine); the H2 antagonists cimetidine and ranitidine had no inhibitory effect. The radioactive colloidal gold technique is a sensitive and reliable tool for pharmacological experiments aimed at investigating the extravasation phenomenon in small tissue samples such as the rat cremaster muscle.