The response of small blood vessels in rat skin and skeletal muscle to repeated application of histamine: a chemical, topographical and electron microscopic study.

Quantitative studies of increased vascular permeability, employing vascular labelling with colloidal carbon and measurement of the rate of escape of intravascular 99Tc labelled antimony sulphide (Sb2S3) colloid, show that local injection of histamine into the skin or cremaster muscle of rats reduces for a period of 6-8 h the leakage induced by a second injection of histamine into the same site. Electron microscope studies employing multiple marker particles show that individual blood vessels are able to respond to two successive applications of histamine, and that the diminished leakage seen after the second injection is due to a reduced response of individual vessels and not to leakage from vessels unaffected by the first injection. Prior administration of bradykinin does not reduce the response to local injection of histamine into rat skin. The result suggest that sustained release of histamine is unlikely to be important in the production of prolonged increase in vascular permeability in acute inflammation. Bradykinin may be involved in such response but the findings provide no evidence for its participation.