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Carmen Campino, Alejandro Martinez-Aguayo, Rene Baudrand, Cristian A. Carvajal, Marlene Aglony, Hernan Garcia, Oslando Padilla, Alexis M. Kalergis, Carlos E. Fardella, Age-Related Changes in 11β-Hydroxysteroid Dehydrogenase Type 2 Activity in Normotensive Subjects, American Journal of Hypertension, Volume 26, Issue 4, April 2013, Pages 481–487, https://doi.org/10.1093/ajh/hps080
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Abstract
Impairment in 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity results in inefficient inactivation of cortisol to cortisone, and it can trigger hypertension through activation of the mineralocorticoid receptor. Information about age-related changes in 11β-HSD2 activity and its physiological consequences is scarce. Our aim was to investigate whether 11β-HSD2 activity is age dependent in normotensive subjects.
We recruited 196 healthy, normotensive subjects. Of these, 93 were children (Group 1: aged 5–15 years), and 103 were adults who were divided according to their ages: Group 2: aged 30–41 years (n = 10); Group 3: aged 42–53 years (n = 72); and Group 4: aged 54–65 years (n = 21). Fasting serum cortisol, cortisone, aldosterone, and plasma renin activity (PRA) were measured. The 11β-HSD2 activity was estimated by the cortisol/cortisone ratio. The results were expressed as median (interquartile range (IQR)) values and compared using Kruskal–Wallis and Dunn’s multiple-comparison tests.
As subject age increased, cortisol concentrations increased (Group 1 median = 8.6, IQR = 6.3–10.8 µg/dl; Group 4 median = 12.4, IQR = 10.7–14.7 µg/dl; P < 0.001), and cortisone concentrations showed a gradual decrease (Group 2 median = 4.0, IQR = 3.3–4.2 µg/dl; Group 4 median =2.8, IQR = 2.6–3.3 µg/dl; P < 0.01). As a consequence, the cortisol/cortisone ratio was higher in the oldest subjects (Group 4) than in the subjects from the other 3 groups; the ratios from Group 4 to Group 1 were 4.4 (IQR = 3.7–5.1) µg/dl, 3.3 (IQR = 2.7–3.8) µg/dl, 2.5 (IQR = 2.3–3.8) µg/dl, and 2.7 (IQR = 2.1–3.4) µg/dl, respectively (P < 0.01). The PRA decreased with age. Blood pressure levels increased with age but stayed within the normal range.
Cortisol and the cortisol/cortisone ratio increased with age, but cortisone decreased, suggesting a decrease in 11β-HSD2 activity. These results suggest that the cortisol-mediated activation of the mineralocorticoid receptor may explain the blood pressure increase in elderly subjects.
