Direct modulation of basal and angiotensin II-stimulated aldosterone secretion by hydrogen ions

Disturbances in acid-base balance in vivo are associated with changes in pl asma aldosteroile concentration, and in vitro changes in extracellular pH ( pH,) influence the secretion of aldosterone by adrenocortical tissue or glo merulosa cells. There is considerable disparity, however, as to the directi on of the effect. Furthermore, the mechanisms by which pH, independently af fects aldosterone secretion or interacts with other secretagogues are not d efined. Thus, bovine glomerulosa cells maintained in primary monolayer cult ure were used to examine the direct effects of pH, on cytosolic free calciu m concentration ([Ca2+](i)) and aldosterone secretion under basal and angio tensin II (AngII)-stimulated conditions, pH(0) was varied from 7.0 to 7.8 ( corresponding inversely to changes in extracellular H+ concentration from 1 6 nM to 100 nM). Whereas an elevation of pH(o) from 7.4 to 7.8 had no consi stent effect, reductions of pH(o) from 7.4 to 7.2 or 7.0 caused proportiona te increases in aldosterone secretion that were accompanied by increases in transmembrane Ca2+ fluxes and [Ca2+](i). These effects were abolished by r emoval of extracellular Ca2+. A decrease in pH(0) from 7.4 to 7.0 also enha nced AngII-stimulated aldosterone secretion. This effect was more pronounce d at low concentrations of AngII and was manifested as an increase in the m agnitude of the secretory response with no effect on potency. In contrast t o its effect on AngII-stimulated aldosterone secretion, a reduction of pH, from 7.4 to 7.0 inhibited the Ca2+ signal elicited by low concentrations (l ess than or equal to 1 x 10(-10)M) of AngII, but did not affect the increas e in [Ca2+](i) caused by a maximal concentration (1 x 10(-8) M) of AngII. T hese data suggest that pH(o) (i.e. H+) has multiple effects on aldosterone secretion. It independently increases aldosterone secretion through a mecha nism involving Ca2+ influx and an increase in [Ca2+](i). Also, it modulates the action of AngII by both decreasing the magnitude of the AngII-stimulat ed Ca2+ signal and increasing the sensitivity of a more distal site to intr acellular Ca2+. The latter action appears to be a more important determinan t in the effects of pH(o) on AngII-stimulated aldosterone secretion.