Results of our previous studies revealed a derangement in the peripheral metabolism of adrenal
steroids in patients with
essential hypertension. To investigate further this finding, all indIVidual free and conjugated metabolites of
cortisol were isolated, identified and quantitated in plasma of 14 normotensive subjects and 13 patients with benign, uncomplicated
essential hypertension, following iv administration of a tracer dose of [4-14-C]
cortisol. In addition, plasma levels of endogenous
cortisol were determined at 8 AM and 4 PM in all the subjects examined. The results obtained revealed the following statistically significant differences between normotensives and hypertensives: 1) Mean plasma concentrations of
cortisol metabolites reduced in ring-A with nonreduced 20-
ketone,
tetrahydrocortisol,
tetrahydrocortisone, and their 5alpha-epimers, were 30% lower in the hypertensives; since these
steroids constitute the bulk of the major group of
cortisol metabolites--the
glucuronide conjugates, plasma levels of this group of conjugates measured in
toto were also found to be significantly lower in the hypertensives. 2) Concentrations of
cortisol metabolites with non-reduced ring-A (delta-4-3-keto configuration preserved) but with reduced 20-
ketone and/or hydroxylated at C-6, 20alpha- and 20beta- dihydrocortisol, 6alpha- and 6beta-hydroxycortisol, and 6-hydroxy-20-dihydrocortisol (all 4 isomers), were 73%, 48% and 68% respectively, higher in the hypertensives; since these
steroids constitute the bulk of the
sulfate-conjugated and
nucleoside-complexed metabolites of
cortisol, plasma levels of these groups of metabolites, measured in
toto, were also found to be higher in the hypertensives. No significant difference was found between normotensives and hypertensives in the AM and PM plasma levels of
cortisol. These findings, in conjunction with the results of our studies on urinary
corticosteroid metabolites, which yielded identical findings, provide evidence for a decreased activity of hepatic
cortisol-delta-4-
hydrogenase enzyme system and increased activities (presumably compensatorily) of
cortisol-20-
reductase and 6-
hydroxylase enzyme systems in patients with
essential hypertension. The interrelation of these findings with those of other investigators studying
steroid metabolites in
hypertension, points to the
corticosteroid metabolizing
enzymes may be an etiological factor in
essential hypertension.