Inhibition of prostacyclin production mediates permissive effect of glucocorticoids on vascular tone. Perturbations of this mechanism contribute to pathogenesis of Cushing's syndrome and Addison's disease.
Glucocorticoids have a permissive effect on vascular tone and blood pressure; they enhance vascular responsiveness to vasopressors such as catecholamines without necessarily having an effect when administered alone. This effect does not require central or systemic mediation. Prostacyclin (prostaglandin I2; PGI2), a potent vasodilator, is produced by the vascular endothelium, vascular smooth muscle cells, adipocytes, and other cells. PGI2 production by vascular endothelium and other cells is decreased by glucocorticoids. The hypothesis is proposed that the effect of glucocorticoids on vascular tone is mediated by inhibition of PGI2 production by vascular endothelium (possibly other cells also). The inhibition of PGI2 production by glucocorticoids may contribute to the hypertension of Cushing's syndrome. Loss of this inhibitory effect in glucocorticoid deficiency states (eg, Addison's disease) may cause enhanced PGI2 production, which may contribute to the haemodynamic and gastrointestinal manifestations of these disorders.
D000224:Addison Disease / Q000209:etiology* / Q000503:physiopathology; D003480:Cushing Syndrome / Q000209:etiology*; D011464:Epoprostenol / Q000096:biosynthesis*; D005938:Glucocorticoids / Q000172:deficiency / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000209:etiology; D008954:Models, Biological; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis*
D005938:Glucocorticoids; D011453:Prostaglandins; D011464:Epoprostenol