Efferent arteriole tubuloglomerular feedback in the renal nephron.
BACKGROUND
Afferent and efferent arteriole resistance exerts critical and opposite actions in the regulation of glomerular capillary pressure (PGC) and glomerular filtration rate (GFR). Tubuloglomerular feedback (TGF) plays an important role in the regulation of afferent arteriole resistance; however, the role of TGF in the regulation of efferent arteriole resistance is less well established. We hypothesized that TGF caused by increased NaCl in the tubular fluid stimulates the macula densa to initiate a cascade of events resulting in efferent arteriole vasodilation, mediated by adenosine via its A2 receptor.


METHODS
Rabbit efferent arterioles and adherent tubular segments with macula densa were simultaneously microperfused in vitro while changing NaCl concentration at the macula densa. To study whether autacoids produced by the glomerulus participate in the effect of TGF on efferent arterioles, they were perfused orthograde or retrograde. To eliminate the hemodynamic influence of the afferent arteriole during orthograde perfusion, the perfusion pipette was advanced to the distal end of the afferent arteriole, and the tip of the pressure pipette was placed beyond the afferent arteriole; for retrograde perfusion, the efferent arteriole was perfused from its distal end.


RESULTS
In efferent arterioles perfused orthograde and preconstricted with norepinephrine (NE), increasing NaCl concentration at the macula densa increased the diameter by 33%. In preconstricted efferent arterioles perfused retrograde, increasing NaCl at the macula densa increased the diameter by 33%. Efferent arteriole vasodilation was completely blocked by a selective adenosine A2 receptor antagonist (3, 7-dimethyl-1-propargylxanthine) but not by an adenosine A1 receptor antagonist (FK838).


CONCLUSIONS
Our data show that in vitro, preconstricted efferent arterioles dilate in response to increased macula densa NaCl, and this process is mediated by activation of adenosine A2 receptors. Thus, TGF changes efferent arteriole resistance in the opposite direction from the afferent arteriole, possibly amplifying TGF regulation of PGC and GFR. In vivo efferent arteriole TGF may only buffer the signals that cause efferent arteriole resistance to parallel changes in afferent arteriole resistance. Effects of TGF on efferent arterioles perfused orthograde or retrograde were similar, suggesting that glomerular autacoids do not participate in this process.
Ren
Y
Y
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Garvin
J L
JL
Carretero
O A
OA
D000818:Animals; D001160:Arterioles / Q000502:physiology; D005246:Feedback / Q000187:drug effects; D007678:Kidney Glomerulus / Q000098:blood supply*; D007684:Kidney Tubules / Q000098:blood supply*; D008297:Male; D009399:Nephrons / Q000098:blood supply*; D010477:Perfusion; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D013805:Theobromine