THE EFFECT OF LOSARTAN POTASSIUM-STIMULATED ALDOSTERONE SECRETION IN-VITRO

Potassium (K+) and angiotensin-II !Ang-II) are two distinct secretagogues for aldosterone release. However, a local adrenal renin-angiotensin system is present, and several studies suggest a complex interaction between K+ and locally produced Ang-II. First, superfusing zona glomerulosa (ZG) cells with K+ stimulates the secretion of both Ang-II and aldosterone. Second, K+-stimulated aldosterone secretion can be reduced in the presence of angiotensin-converting enzyme inhibitors. Because angiotensin-converting enzyme inhibitors are not specific inhibitors of the adrenal renin-angiotensin system, we further tested the hypothesis that locally produced Ang-II participates in K+-stimulated aldosterone release from rat ZG cells by using a specific Ang-II antagonist. Although type 1 (AT(1)) and type 2 (AT(2)) Ang-II receptors are present in ZG cells, only AT(1) antagonist has been shown to mediate Ang-II-induced aldosterone secretion. Losartan, a specific AT(1) antagonist, was used in this study. In the presence of losartan (10 mu M for 9 mM K+ and 100 mu M for 5 mM K+), the average aldosterone secretion during 2 h of superfusion with 9 mM K+ and 5 mM K+ was 70.1+/-5.4% (n = 5) and 58.5+/-2.2% (n = 3), respectively, of that in its absence. Losartan did not alter the amount of Ang-II secreted. The inhibitory effect of losartan lasted longer than 60 min after it was terminated. In summary, our results support the hypothesis that locally produced Ang-II contributes to the aldosterone secretory response to KC stimulation at both physiological and supraphysiological levels.