(Hypertension. 2000;35:1099.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Role of 11ß-Hydroxysteroid Dehydrogenase in Nongenomic Aldosterone Effects in Human Arteries
From the Laboratory of Cellular and Molecular Physiology, Faculty of Medicine, University of Los Andes, Las Condes, Santiago, Chile.
Correspondence to Dr Elisa T. Marusic, Laboratory of Cellular and Molecular Physiology, Faculty of Medicine, University of Los Andes, San Carlos Apoquindo 2200, Las Condes, Santiago 6782468, Chile. E-mail emarusic{at}uandes.cl
Abstract—The aim of the present study was to demonstrate rapid effects of aldosterone on the Na+-H+ exchanger in strips of human vascular vessels and to determine whether 11ß-hydroxysteroid dehydrogenase enzyme (11ß-HSD) could play a protective role in this response, such as that described for the classic type I mineralocorticoid receptor (MR). The activity of 11ß-HSD isoforms 1 and 2 were measured in fetal and adult arteries. Both isoforms are present in adult and fetal vessels. However, a significant difference in the proportion of each isoform was found. Isoform 1 activity (in pmol · min-1 · 100 mg-1 protein) was 42±5 in fetal vessels and 29±2 in adult arteries, and isoform 2 activity was 78±7 in fetal and 12±2 in adult tissue. The nongenomic effect of aldosterone on Na+-H+ exchanger activity was measured in strips of chorionic and radial uterine arteries loaded with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein. Recordings of intracellular pH (pHi) were made by videofluorescence microscopy. Aldosterone (0.5 nmol/L) rapidly increased pHi, with a half-maximal effect between 2 and 3 nmol/L in both fetal and adult vessels. Ethylisopropylamiloride, a specific inhibitor of the Na+-H+ exchanger, inhibited this effect. The hormone-mediated increase in pHi was unaffected by spironolactone, a classic antagonist of MR, but was completely blocked by RU28318. Cortisol (up to 1 µmol/L) had no effect on pHi, but when applied in the presence of carbenoxolone, a dramatic increase in Na+-H+ exchanger activity was evident. The increments on pHi for each cortisol concentration were similar to those observed for aldosterone. These findings suggest that vascular 11ß-HSD plays an active role in maintaining the specificity of the rapid effects of aldosterone.
Key Words: nongenomic • human • muscle, smooth, vascular • sodium-hydrogen antiporter • aldosterone • 11ß-hydroxysteroid dehydrogenase • cortisol
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