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

Am J Physiol Renal Physiol. 2007 Jul;293(1):F110-20. doi: 10.1152/ajprenal.00516.2006. Epub 2007 Mar 13.

Abstract

The proximal tubule (PT) is major site for the reabsorption of filtered HCO(3)(-). Previous work on the rabbit PT showed that 1) increases in basolateral (BL) CO(2) concentration ([CO(2)](BL)) raise the HCO(3)(-) reabsorption rate (J(HCO(3))), and 2) the increase that luminal angiotensin II (ANG II) produces in J(HCO(3)) is greatest at 0% [CO(2)](BL) and falls to nearly zero at 20%. Here, we investigate the role of angiotensin receptors in the [CO(2)](BL) dependence of J(HCO(3)) 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 J(HCO(3)) (5% CO(2)) to the value normally seen at 0% in the absence of inhibitors and eliminates the J(HCO(3)) response to changes in [CO(2)](BL). However, basolateral 10(-8) M saralasin has no effect. As with saralasin, luminal 10(-8) M candesartan (AT(1) antagonist) reduces baseline J(HCO(3)) and eliminates the [CO(2)](BL) dependence of J(HCO(3)). Luminal 10(-7) M PD 123319 (AT(2) antagonist) has no effect. Finally, we compared PTs from wild-type and AT(1A)-null mice of the same genetic background. Knocking out AT(1A) modestly lowers baseline J(HCO(3)) and, like luminal saralasin or candesartan in rabbits, eliminates the J(HCO(3)) response to changes in [CO(2)](BL). Our accumulated evidence suggests that ANG II endogenous to the PT binds to the apical AT(1A) receptor and that this interaction is critical for both baseline J(HCO(3)) and its response to changes in [CO(2)](BL). Neither apical AT(2) receptors nor basolateral ANG II receptors are involved in these processes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Benzimidazoles / pharmacology
  • Bicarbonates / metabolism*
  • Carbon Dioxide / pharmacology*
  • Data Interpretation, Statistical
  • Female
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Mice
  • Mice, Knockout
  • Perfusion
  • Rabbits
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / physiology*
  • Saralasin / pharmacology
  • Signal Transduction / drug effects
  • Tetrazoles / pharmacology

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Bicarbonates
  • Receptor, Angiotensin, Type 1
  • Tetrazoles
  • Carbon Dioxide
  • Saralasin
  • candesartan