Physiological regulation of vascular permeability by endogenous glucocorticoids and active oxygen

A copper chelator, diethyldithiocarbamate (DDC), injection and adrenalectomy induce significant paw swelling by low doses of serotonin, histamine, or bradykinin, which can result in mild swelling in non-treated mice. Dexamethasone, Cu,Zn-superoxide dismutase (SOD), and hydroxyl radical scavengers suppressed the DDC-provoked edema, but only dexamethasone suppressed the edema of adrenalectomized mice. Adrenal stimulation by SOD is exclusive in that the suppression of edema by SOD began about 1 h prior to that by glucocorticoid. In order to explain the data obtained, the existence of a vascular permeability inhibitory protein (called "vasoregulin") was assumed. This protein must be synthesized constantly somewhere in the body and continuously inactivated by active oxygen in vivo. Local levels of vasoregulin may limit the responses of vascular permeability against the chemical mediators. This hypothesis was also supported by the edema-enhancing effects of protein/RNA synthesis inhibitors.