Significance of 19-noraldosterone, a new mineralocorticoid, in clinical and experimental hypertension.

19-Noraldosterone, which was recently shown to be synthesized and produced in the human adrenal gland, possesses potent mineralocorticoid and hypertensinogenic activities. 18,19-Dihydroxycorticosterone (18,19-(OH)2-B) and 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B), a possible precursor of 19-noraldosterone, have been identified in human urine. These mineralocorticoid hormones are regulated by the renin-angiotensin system and synthesized in adrenal glomerulosa cells. Urinary 19-noraldosterone correlated with urinary 18,19-(OH)2-B, 18-OH-19-nor-B, 18-hydroxycorticosterone (18-OH-B), and aldosterone. Urinary excretion of 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B were increased in patients with aldosterone-producing adenoma (APA) and in those with idiopathic hyperaldosteronism (IHA), but the two did not differ significantly. Urinary 18-OH-B and 18-hydroxycortisol (18-OH-F) were significantly higher in APA compared with IHA. Though urinary 18-OH-F and 18-OH-B concentrations were useful markers, urinary 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B could not be used to distinguish the two subsets of primary aldosteronism. Urinary 19-noraldosterone did not differ in hypertensive and normotensive patients. However, urinary 19-noraldosterone was increased in some hypertensive patients. In spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP), urinary 19-noraldosterone was increased at the prehypertensive stage compared with Wistar-Kyoto (WKY) rats. Urinary 19-noraldosterone was decreased in 9-week-old SHR and SHRSP compared with WKY rats. However urinary 19-noraldosterone was higher in SHRSP than in SHR. These elevated levels of 19-noraldosterone may contribute to hypertension in some individuals and in experimental hypertensive rats.