5 alpha-Dihydro-11-deoxycorticosterone: effect on blood pressure in the rat

The bioactivity of 5 alpha-reduced sex steroids such as 5 alpha-dihydrotestosterone has increased interest in an analogous role for 5 alpha-reduced mineralocorticoids in hypertensive syndromes. In view of its relatively high mineralocorticoid receptor affinity despite relatively low electrolyte-altering effects, 5-alpha-dihydro-11-deoxycorticosterone, or 5 alpha DHDOC (2) was compared to 11-deoxycorticosterone acetate (DOCA) for blood pressure-altering ability by continuous subcutaneous infusion into uninephrectomized saline-drinking Sprague-Dawley male rats, at doses selected on the basis of relative mineralocorticoid receptor affinity. After three weeks of treatment, DOCA significantly raised blood pressure, body weight, heart and kidney weight, and produced a discernible increase in fluid intake; 5 alpha DHDOC failed to affect any of these parameters commonly influenced by mineralocorticoids. We conclude that 1) the ability of 5 alpha DHDOC to affect blood pressure was not predicted by its relatively high affinity for the mineralocorticoid receptor, and 2) these data do not support a role for 5 alpha DHDOC in mineralocorticoid hypertension, although differences in protein binding and clearance could affect its blood pressure-altering activity.