Long-term regulation of proximal tubule acid-base transporter abundance by angiotensin II

S. Turban, K. T. Beutler, R. G. Morris, S. Masilamani, R. A. Fenton, M. A. Knepper, R. K. Packer

Research output: Contribution to journalArticlepeer-review

Abstract

In the proximal tubule, angiotensin II (Ang-II) regulates HCO -3 reabsorption and H+ secretion by binding the type 1 Ang-II (AT1) receptor, stimulating Na+/HCO- 3 cotransport and Na+/H+ exchange. Studies were carried out to determine if long-term changes in Ang-II receptor occupation alter the abundance of the basolateral Na+/HCO- 3 cotransporter (NBC1) or the apical membrane type 3 Na +/H+ exchanger (NHE3). In the first set of experiments, rats eating a low-sodium diet were infused with the AT1 blocker, candesartan, or vehicle. In the second, lisinopril-infused rats were infused with either Ang II or vehicle. Transporter abundances were determined in whole kidney homogenates (WKH) and in brush border membrane (BBM) preparations by semiquantitative immunoblotting. Tissue distribution of transporters was assessed by immunocytochemistry. Blockade of the AT1 receptor by candesartan caused decreased abundance of NBC1 in WKH (59±9% of control; P<0.05) and Ang-II infusion increased abundance (130±7% of control; P<0.05). Changes in NBC1 in response to candesartan were confirmed immunohistochemically. Neither candesartan nor Ang II infusion affected the abundance of NHE3 in WKH or cortical homogenates. Candesartan decreased type 2 sodium-phosphate cotransporter abundance in both WKH (52±7% of control; P<0.05) and BBM (32±7% of control; P<0.05). Serum bicarbonate was decreased by candesartan and increased by Ang-II. Candesartan also decreased urinary ammonium excretion (P<0.05). The long-term effects of Ang-II in the proximal tubule may be mediated in part by regulation of NBC1 abundance, modifying bicarbonate reabsorption.

Original languageEnglish (US)
Pages (from-to)660-668
Number of pages9
JournalKidney international
Volume70
Issue number4
DOIs
StatePublished - Aug 28 2006
Externally publishedYes

Keywords

  • AT1
  • Acid-base
  • Candesartan
  • NBC1
  • NHE3
  • NaPi-2

ASJC Scopus subject areas

  • Nephrology

Fingerprint

Dive into the research topics of 'Long-term regulation of proximal tubule acid-base transporter abundance by angiotensin II'. Together they form a unique fingerprint.

Cite this