| Abstrakt: |
The acute direct action of angiotensin-( 1-7) [ANG-(1-7)] on bicarbonate reabsorption (JHCO3 -) was evaluated by stationary microperfusions on in vivo middle proximal tubules in rats using H ion-sensitive microelectrodes. The control JHCO3 - is 2.82 ± 0.078 nmol·cm-2·s-1 (50). ANG-(1-7) (10-12 or 10-9 M) in luminally perfused tubules decreases JHCO3 - (36 or 60%, respectively), but ANG-(1-7) (10-6 M) increases it (80%). A779 increases JHCO3 - (30%) and prevents both the inhibitory and the stimulatory effects of ANG-(1-7) on it. S3226 decreases JHCO3 - (45%) and changes the stimulatory effect of ANG-(1-7) to an inhibitory effect (30%) but does not affect the inhibitory effect of ANG- (1-7). Our results indicate that in the basal condition endogenous ANG-(1-7) inhibits JHCO3 - and that the biphasic dose-dependent effect of ANG-(1-7) on JHCO3 - is mediated by the Mas receptors via the Na+/H+ exchanger 3 (NHE3). The control value of intracellular Ca2+ concentration ([Ca2+]i), as monitored using fura-2 AM, is 101 ± 2 nM (6), and ANG-(1-7) (10-12, 109-, or 106-M) transiently (3 min) increases it (by 151, 102, or 52%, respectively). A779 increases the [Ca2+]i (25%) but impairs the stimulatory effect of all doses of ANG-(1-7) on it. The use of BAPTA or thapsigargin suggests a correlation between the ANG-(1-7) dose-dependent effects on [Ca2+]i and JHCO3 -. Therefore, the interaction of the opposing dose-dependent effects of ANG II and ANG-(1-7) on [Ca2+]i and JHCO3 - may represent an physiological regulatory mechanism of extracellular volume and/or pH changes. However, whether [Ca2+]i modification is an important direct mechanism for NHE3 activation by these peptides or is a side effect of other signaling pathways will require additional studies. [ABSTRACT FROM AUTHOR] |
