Corticosteroids and the generalized Shwartzman reaction. Mechanisms of sensitization in the rabbit

Abstract

An analysis of the effects of adrenal cortical steroids on the response of the vascular system to bacterial endotoxin has shown that glucocorticoids (cortisone, triamcinolone) are capable of preparing the system for the generalized Shwartzman reaction. On the other hand, the mineralocorticoid desoxycorticosterone acetate does not have this capability. The mechanism of preparation by glucocorticoids has been studied. Administering insulin, with maintenance of normal blood sugar, had no effect on the extent of glomerular capillary thrombosis. Blockade, however, of alpha-adrenergic receptor sites by Dibenzyline caused a significant reduction of the thrombosis. In addition, cortisone-treated animals did not require exogenous stimulation of alpha-adrenergic receptor sites by norepinephrine to localize thrombi in the glomerular capillaries when Hageman factor was activated (by ellagic acid) and fibrinolysis inhibited (by epsilon-aminocaproic acid). It is concluded that glucocorticoids prepare for the generalized Shwartzman reaction by increasing the sensitivity of the microcirculation to stimulation of alpha-adrenergic receptor sites.