Role of the AT1A receptor in the CO2-induced stimulation of HCO3− reabsorption by renal proximal tubules

Abstract

The proximal tubule (PT) is major site for the reabsorption of filtered HCO3−. Previous work on the rabbit PT showed that 1) increases in basolateral (BL) CO2 concentration ([CO2]BL) raise the HCO3− reabsorption rate ( JHCO3), and 2) the increase that luminal angiotensin II (ANG II) produces in JHCO3 is greatest at 0% [CO2]BL and falls to nearly zero at 20%. Here, we investigate the role of angiotensin receptors in the [CO2]BL dependence of JHCO3 in isolated perfused PTs. We found that, in rabbit S2 PT segments, luminal 10−8 M saralasin (peptide antagonist of ANG II receptors), lowers baseline JHCO3 (5% CO2) to the value normally seen at 0% in the absence of inhibitors and eliminates the JHCO3 response to changes in [CO2]BL. However, basolateral 10−8 M saralasin has no effect. As with saralasin, luminal 10−8 M candesartan (AT1 antagonist) reduces baseline JHCO3 and eliminates the [CO2]BL dependence of JHCO3. Luminal 10−7 M PD 123319 (AT2 antagonist) has no effect. Finally, we compared PTs from wild-type and AT1A-null mice of the same genetic background. Knocking out AT1A modestly lowers baseline JHCO3 and, like luminal saralasin or candesartan in rabbits, eliminates the JHCO3 response to changes in [CO2]BL. Our accumulated evidence suggests that ANG II endogenous to the PT binds to the apical AT1A receptor and that this interaction is critical for both baseline JHCO3 and its response to changes in [CO2]BL. Neither apical AT2 receptors nor basolateral ANG II receptors are involved in these processes.