Role of 11β-Hydroxysteroid Dehydrogenase in Nongenomic Aldosterone Effects in Human Arteries

Author:

Alzamora Rodrigo1,Michea Luis1,Marusic Elisa T.1

Affiliation:

1. From the Laboratory of Cellular and Molecular Physiology, Faculty of Medicine, University of Los Andes, Las Condes, Santiago, Chile.

Abstract

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 11β-hydroxysteroid dehydrogenase enzyme (11β-HSD) could play a protective role in this response, such as that described for the classic type I mineralocorticoid receptor (MR). The activity of 11β-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 μmol/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 11β-HSD plays an active role in maintaining the specificity of the rapid effects of aldosterone.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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