Role of 11 beta-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries

Alzamora, R; Michea, L.; Marusic, ET


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 11 beta-hydroxysteroid dehydrogenase enzyme (11 beta-HSD) could play a protective role in this response, such as that described for the classic type I mineralocorticoid receptor (MR). The activity of 11 beta-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 (pH(i)) were made by videofluorescence microscopy. Aldosterone (0.5 nmol/L) rapidly increased pH(i), 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 pH(i) was unaffected by spironolactone, a classic antagonist of MR, but was completely blocked by RU28318. Cortisol (up to 1 mu mol/L) had no effect on pH(i), but when applied in the presence of carbenoxolone, a dramatic increase in Na+-H+ exchanger activity was evident. The increments on pH(i) for each cortisol concentration were similar to those observed for aldosterone. These findings suggest that vascular 11 beta-HSD plays an active role in maintaining the specificity of the rapid effects of aldosterone.

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Título según WOS: Role of 11 beta-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries
Título de la Revista: HYPERTENSION
Volumen: 35
Número: 5
Fecha de publicación: 2000
Página de inicio: 1099
Página final: 1104
Idioma: English
Notas: ISI