The effect of losartan on 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 (AT1) and type 2 (AT2) Ang-II receptors are present in ZG cells, only AT1 antagonist has been shown to mediate Ang-II-induced aldosterone secretion. Losartan, a specific AT1 antagonist, was used in this study. In the presence of losartan (10 microM for 9 mM K+ and 100 microM 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 K+ stimulation at both physiological and supraphysiological levels.
Chiou
C Y
CY
Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Kifor
I
I
Moore
T J
TJ
Williams
G H
GH
D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D010507:Periodicity; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D019808:Losartan; D011188:Potassium