Effect of dietary sodium (Na+) on urinary 6-beta-hydroxycortisol excretion in salt-sensitive (SS) and salt-resistant (SR) adolescent African-Americans.

Cortisol (F) is the substrate for family 3A cytochrome P-450 enzyme (CYP3A) conversion to 6β-hydroxycortisol (6β-OH-F). Urinary 6β-OH-F/free F ratio is a proposed index of in vivo CYP3A activity. Preliminary studies have suggested the presence of an increased ratio in a subset of African-American essential hypertensives. Correlations between renal CYP3A activity and blood pressure (BP) with variation in age, strain and drug treatment in the spontaneously hypertensive rat are also consistent with a role of CYP3A in the pathogenesis of BP elevation in this genetic model. We have evaluated the urinary excretion of 6β-OH-F in a previously characterized subset of adolescent normotensive African-Americans determined to be SS or SR. Adolescents were classified as SS if their mean BP increased >5 mm Hg from a 5 day low Na+ diet (50 mEq/24hr) to a 10 day high Na+ diet (NaCl SUPPLEMENT =150 mEq/24hr). 6β-OH-F was measured by uv absorbance on reverse phase HPLC with pre-extraction of urine on two cartridges (reverse and normal phase, sequentially) and is reported as μcg/24 hrs. In the SS group subjects increased 6β-OH-F while in the SR group decreased 6 β-OH-F upon dietary Na+ change. Increased 6β-hydroxylation of steroids could play a role in susbsequent BP elevation in SS African-American adolescents. Future studies will determine whether increased CYP3A activity or concentration of substrate accounts for increased urinary excretion of 6β-OH-F in SS subjects, upon going from a low to high sodium diet.