19-Nor-corticosteroids in experimental and human hypertension

Recent reports demonstrate that the 19-nor-corticosteroids (19-nor-DOC) are naturally-occurring substances in hypertensive animal models as well as man. Since some 19-nor-corticosteroids are potent mineralocorticoids, they may have a role in regulating systemic arterial pressure and be involved in the pathogenesis of hypertension. This paper reports the probable biosynthetic pathway, factors regulating the secretion or production, and measurement of 19-nor-DOC in man and the spontaneously hypertensive rat (SHR). These studies demonstrate (1) 19-nor-DOC is greatly influenced by ACTH and dexamethasone but less so by high and low salt diets in normotensive subjects; (2) 19-nor-DOC is greatly increased in some but not all hypertensive patients; (3) 19-nor-DOC is increased in prehypertensive SHR compared to WKY rats. The likelihood of metacorticoid hypertension and possible role of other 19-nor-corticosteroids, including 19-nor-progesterone, are discussed. It can be concluded that 19-nor-corticosteroids are synthesized by extra-adrenal tissues in biologically active quantities. They are increased and possibly pathogenetic in certain states of human and experimental hypertension.