Evidence that angiotensin-II and potassium collaborate to increase cytosolic calcium and stimulate the secretion of aldosterone.

Abstract

Angiotensin-II (AII) and potassium (K+) as stimuli of aldosterone secretion enhance each other's stimulatory potential. In the present study we looked for evidence that AII and K+ act through a common mechanism of signal transduction to affect secretion. Bovine adrenal glomerulosa cells were loaded with the calcium (Ca2+) probe aequorin to permit detection over prolonged time periods of the changes in cytosolic Ca2+ that occur in response to AII and K+. Perfusion fractions were collected for simultaneous measurement of aldosterone production rates. AII (10(-7) M) produced an immediate and transient increase in Ca2+, followed by a Ca2+ plateau that remained above baseline for as long as AII was present. An increase in K+ concentration (from 5 to 12 mM) produced a slow and eventually sustained increase in cytosolic Ca2+, which resembled the plateau produced by AII. Nitrendipine (10(-5) M) completely inhibited the secretory response to AII and K+ (during 60-min incubations) and inhibited the typical K+-induced increase in Ca2+. The sustained increase in Ca2+ with AII (the plateau) required extracellular Ca2+ and was proportional to the prevailing extracellular K+ concentration. When glomerulosa cells were incubated with AII, the aldosterone secretory response to K+ was substantially enhanced (P less than 0.001). In summary, stimulation by both AII and K+ resulted in a sustained increase in Ca2+ influx. AII-induced Ca2+ influx was dependent on the ambient K+ concentration. These results indicate that AII and K+ act together to determine the optimal rate of Ca2+ entry, which may then lead to the appropriate secretory rate of aldosterone.