Steroids during development of genetic hypertension in rats of Lyon strain

The urinary excretion and the plasma concentration of deoxycorticosterone (DOC), corticosterone, 18-hydroxy-DOC (18-OH-DOC), aldosterone, and 19-nor-DOC were measured by specific radioimmunoassays in genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) male rats of the Lyon strains at two ages that characterize the development of their systolic blood pressure (SBP). When compared with both LN and LL controls, 5-wk-old LH rats exhibited an increased urinary DOC and decreased urinary corticosterone excretions, which were significantly related to the SBP level (r' = 0.618 and -0.520; n = 23; P less than 0.01 for DOC and corticosterone, respectively). In addition, the adrenal synthesis of LH rats was found to rely on an increased 18-hydroxylase activity as indicated by elevated urinary 18-OH-DOC/corticosterone and aldosterone/corticosterone associated with a lower 11-beta-hydroxylase activity shown by the decreased urinary corticosterone/DOC. Twenty-wk-old LH rats with fully developed hypertension exhibited normal urinary excretion of steroids and a decrease in plasma DOC concentration, which negatively correlated with the SBP level (r' = -0.574; n = 25; P less than 0.01). In conclusion, the present study demonstrates that in the Lyon model of genetically hypertensive rats, compared with two genetically different control strains and maintained under physiological unstressed conditions, the development of hypertension is associated with an increased urinary excretion of DOC. After the full development of their hypertension, the mineralocorticoid synthesis in LH rats returns to normal or low levels which could, however, remain inappropriately high for their sodium body content.