| 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) (10−12or 10−9M) in luminally perfused tubules decreases JHCO3−(36 or 60%, respectively), but ANG-(1–7) (10−6M) 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, 10−9, or 10−6M) 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+]iand JHCO3−. Therefore, the interaction of the opposing dose-dependent effects of ANG II and ANG-(1–7) on [Ca2+]iand JHCO3−may represent an physiological regulatory mechanism of extracellular volume and/or pH changes. However, whether [Ca2+]imodification is an important direct mechanism for NHE3 activation by these peptides or is a side effect of other signaling pathways will require additional studies. |
