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Salt Loading Affects Cortisol Metabolism in Normotensive Subjects: Relationships with Salt Sensitivity

Departments of Endocrinology (M.N.K., W.J.S., R.P.F.D.) and Nephrology (F.G.H.V.D.K., A.H.B., G.N.) and Laboratory Center (J.K.), University Hospital Groningen, 9700 RB Groningen, The Netherlands

Address all correspondence and requests for reprints to: M. N. Kerstens, M.D., Department of Endocrinology, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: m.n.kerstens{at}int.azg.nl.

We studied cortisol metabolism together with insulin sensitivity [homeostatic model assessment (HOMA)] and renal hemodynamics in 19 salt-resistant (sr) and nine salt-sensitive (ss) normotensive subjects after a low- and high-salt diet. Results are described as high- vs. low-salt diet. Sum of urinary cortisol metabolite excretion (_metabolites) increased in sr subjects (3.8 ± 1.6 vs. 3.1 ± 1.1 µg/min per square meter, P < 0.05) and decreased in ss subjects (2.3 ± 1.0 vs. 2.9 ± 1.1 µg/min per square meter, P < 0.05). Plasma 0830 h cortisol decreased in sr subjects but did not change significantly in ss subjects. In all subjects, the absolute blood pressure change correlated negatively with the percentage change in _metabolites (P < 0.05) and positively with the percentage change in renal vascular resistance (P < 0.05). _metabolites during high-salt diet correlated negatively with the percentage changes in plasma 0830 h cortisol (P < 0.05) and renal vascular resistance (P = 0.05). HOMA did not change in either group, but the percentage change in HOMA correlated positively with the percentage change in plasma cortisol (P = 0.001) and negatively with the percentage change in _metabolites (P < 0.01). Parameters of 11ß-hydroxysteroid dehydrogenase activity were not different between groups and did not change. In conclusion, these data suggest that cortisol elimination is affected differently after salt loading in sr and ss subjects. Changes in circulating cortisol might contribute to individual sodium-induced alterations in insulin sensitivity.

This work was supported by grants (97-27 and 01-13) from the J. K. de Cock Foundation, Groningen, The Netherlands.

Abbreviations: allo-THF, Allo-tetrahydrocortisol; ERPF, effective renal plasma flow; HOMA, homeostatic model assessment; 11ßHSD, 11ß-hydroxysteroid dehydrogenase; MAP, mean arterial blood pressure; RVR, renal vascular resistance; sr, salt-resistant; ss, salt-sensitive; THE, tetrahydrocortisone; THF, tetrahydrocortisol; UFE, urinary free cortisone; UFF, urinary free cortisol.