Possible role of adenosine in macula densa control of glomerular hemodynamics

Yi Lin Ren, Shuji Arima, Oscar A. Carretero, Sadayoshi Ito

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background. The macula densa (MD), a plaque of specialized tubular epithelial cells, senses changes in tubular NaCl concentration and sends a signal(s) that controls the resistance of the glomerular afferent arteriole (Af-Art). This mechanism, called tubuloglomerular feedback (TGF), is thought to be important in the homeostasis of body fluids and electrolytes. Our aim was to determine the range of NaCl concentrations in tubular fluid at the MD that would elicit the Af-Art response. In addition, we examined the possible involvement of adenosine in transmitting the signal from the MD to the Af-Art. Methods. Rabbit Af-Arts and attached MD were simultaneously microperfused in vitro, keeping pressure in the Af-Art at 60 mm Hg. Results. Increasing the Na+/Cl- concentration of the MD perfusate from 26/7 to 41/22 mEq/L decreased the luminal diameter of the terminal Af-Art segment by 10 ± 4% (N = 9; P < 0.01). The response was maximal at 55/36 mEq/L (18 ± 6%), so that further elevation of NaCl concentration had no additional effect (20 ± 6% at 84/65 mEq/L). When FK838 (10-6 mol/L), a specific adenosine A1 receptor antagonist, was added to both Af-Art perfusate and bath, Af-Art constriction was completely abolished. The maximum response was 20 ± 3% before FK838 and 0.6 ± 1% afterward (N = 12). Adding adenosine at 10-8 mol/L to both bath and perfusate significantly augmented Af-Art constriction induced by increased NaCl at the MD (P < 0.01); however, adding 10-8 to 10-6 mol/L adenosine to the MD perfusate had no effect regardless of the NaCl concentration at the MD. Conclusions. These results demonstrate that MD control of Af-Art resistance is induced by relatively low NaCl concentrations at the MD, and that activation of the adenosine A1 receptor in the vascular and interstitial space (but not the tubular lumen) may be essential for signal transmission from the MD to the Af-Art.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalKidney international
Volume61
Issue number1
DOIs
Publication statusPublished - 2002 Jan 1

Keywords

  • Adenosine A receptor
  • Afferent arteriole
  • Microperfusion
  • Tubuloglomerular feedback

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Possible role of adenosine in macula densa control of glomerular hemodynamics'. Together they form a unique fingerprint.

  • Cite this