Intravenous injection of horseradish peroxidase in the rat stimulates corticosterone and adrenocorticotropic hormone release.

Wistar rats were given intravenous (i.v.) horseradish peroxidase (HRP) in saline in doses commonly used to study vascular permeability and the blood-brain barrier. Samples of blood were taken from conscious animals via indwelling catheters at intervals up to 6 h after the HRP injection. Plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone were determined and compared with levels in control rats injected with saline alone. Rats injected with saline only presented levels of hormones within the low limits of normal indicating an insignificant influence of stress induced by the experimental procedure. Within 30 min of the i.v. HRP injection, the plasma concentrations of both ACTH and corticosterone increased to very high levels and remained so throughout the period of observation, namely 6 h. The time course of the changes in the concentrations was the same for the two hormones and the actual numerical values were related to the dose of HRP injected. The i.v. injection of HRP in Wistar rats, therefore, induces a marked release of stress hormones which by themselves have profound physiological effects. This phenomenon must be taken into account, in studies on normal vascular permeability using HRP as a tracer and also in similar experiments exploring various pathological conditions of the blood-brain barrier.