Direct action of aldosterone on bicarbonate reabsorption in in vivo cortical proximal tubule

Abstract

The direct action of aldosterone (10−12M) on net bicarbonate reabsorption ( JHCO3−) was evaluated by stationary microperfusion of an in vivo middle proximal tubule (S2) of rat kidney, using H ion-sensitive microelectrodes. Aldosterone in luminally perfused tubules caused a significant increase in JHCO3−from a mean control value of 2.84 ± 0.08 [49/19 ( n° of measurements/ n° of tubules)] to 4.20 ± 0.15 nmol·cm−2·s−1(58/10). Aldosterone perfused into peritubular capillaries also increased JHCO3−, compared with basal levels during intact capillary perfusion with blood. In addition, in isolated perfused tubules aldosterone causes a transient increase of cytosolic free calcium ([Ca2+]i), monitored fluorometrically. In the presence of ethanol (in similar concentration used to prepare the hormonal solution), spironolactone (10−6M, a mineralocorticoid receptor antagonist), actinomycin D (10−6M, an inhibitor of gene transcription), or cycloheximide (40 mM, an inhibitor of protein synthesis), the JHCO3−and the [Ca2+]iwere not different from the control value; these drugs also did not prevent the stimulatory effect of aldosterone on JHCO3−and on [Ca2+]i. However, in the presence of RU 486 alone [10−6M, a classic glucocorticoid receptor (GR) antagonist], a significant decrease on JHCO3−and on [Ca2+]iwas observed; this antagonist also inhibited the stimulatory effect of aldosterone on JHCO3−and on [Ca2+]i. These studies indicate that luminal or peritubular aldosterone (10−12M) has a direct nongenomic stimulatory effect on JHCO3−and on [Ca2+]iin proximal tubule and that probably GR participates in this process. The data also indicate that endogenous aldosterone stimulates JHCO3−in middle proximal tubule.