The aim of the present study was to demonstrate rapid effects of aldosterone on the Na ϩ -H ϩ exchanger in strips of human vascular vessels and to determine whether 11␤-hydroxysteroid dehydrogenase enzyme (11␤-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␤-HSD isoforms 1 and 2 were measured in fetal and adult arteries. Both isoforms are present in adult and fetal vessels. However, a

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... t difference in the proportion of each isoform was found. Isoform 1 activity (in pmol ⅐ min Ϫ1 ⅐ 100 mg Ϫ1 protein) was 42Ϯ5 in fetal vessels and 29Ϯ2 in adult arteries, and isoform 2 activity was 78Ϯ7 in fetal and 12Ϯ2 in adult tissue. The nongenomic effect of aldosterone on Na ϩ -H ϩ exchanger activity was measured in strips of chorionic and radial uterine arteries loaded with the pH-sensitive dye 2Ј,7Ј-bis(2-carboxyethyl)-5,6carboxyfluorescein. 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 ϩ -H ϩ 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 mol/L) had no effect on pH i , but when applied in the presence of carbenoxolone, a dramatic increase in Na ϩ -H ϩ 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␤-HSD plays an active role in maintaining the specificity of the rapid effects of aldosterone. (Hypertension. 2000;35:1099-1104.)