title: Possible role of adenosine in macula densa control of glomerular hemodynamics.
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.
authors.affiliation: Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA. deanw59@hotmail.com
authors.forename: Yilin
authors.initials: Y
authors.lastname: Ren
authors.forename: Shuji
authors.initials: S
authors.lastname: Arima
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Carretero
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007606:Juxtaglomerular Apparatus / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018715:Microscopy, Video; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011725:Pyridines; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; C102861:FK 838; D012965:Sodium Chloride; D000241:Adenosine