Hypertensinogenic Activities of Ring A-Reduced Metabolites of Aldosterone

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 8; no. 4, Part 2 Suppl I; pp. I-187 - I-190
• Main Authors: GORSLINE, JANE, HARNIK, MARCEL, TRESCO, PATRICK A, MORRIS, DAVID J
• Format: Journal Article
• Language: English
• Published: American Heart Association, Inc 01-04-1986
• ISSN: 0194-911X; 1524-4563

Spontaneously hypertensive rats (SHR) were adrenalectomized at 6 weeks of age and received subcutaneous implants of mini-osmotic pumps, loaded with vehicle alone (sham pumps), aldosterone, or ring A-rcduced metabolites of aldosterone (3α,5α-tetrahydroaldosterone; 5α-dihydroaldosterone; 3β15α-tetrahydroaldosterone; or 3α,5β-tetrahydroaldosterone. The control adrenalectomized SHR (sham pumps) maintained low, normotensive levels of blood pressure during the 2-week experiment. In contrast, continuous infusions of very low dosages of aldosterone (0.1–1.0 μg/day) caused dose-dependent increases in blood pressure. Each of the reduced metabolites of aldosterone that were tested also caused a significant increase in blood pressure in adrenalectomized SHR; their relative hypertensinogenic potencies were 3α,5α-tetrahydroaldosterone > 5α-dihydroaldosterone > > 3β15α-tetrahydroaldosterone = 3α,5β-tetrahydroaldosterone. High levels of plasma renin activity measured in control adrenalectomized SHR (sham pumps) were fully suppressed following infusions of aldosterone (0.5 μg/day) and the higher dosages of 3α,5αtetrahydroaldosterone and 5α-dihydroaldosterone (25 and 50 μg/day). Little or no change in plasma renin activity levels was seen, however, with either 3β15α-tetrahydroaldosterone or 3α,5β-tetrahydroaldosterone infusions. These experiments indicate that 1) adrenalectomized SHR are extremely sensitive to constant infusions of very small quantities of the mineralocorticoid aldosterone, and 2) several of the ring-A-reduced metabolites of aldosterone also possess significant hypertensinogenic activity.