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Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112-2699
Adenosine
vasoconstricts preglomerular arterioles via adenosine A1
receptors. Because adenosine also activates adenosine A2
receptors, its overall renal vascular actions are complex and not fully
understood. The present study was performed to determine the relative
contributions of adenosine A1 and A2a receptors
to the responsiveness of the renal microvasculature to adenosine. Afferent and efferent arteriolar diameters were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. Basal
afferent and efferent arteriolar diameters averaged 17.1 ± 0.5 (n = 35) and 17.8 ± 0.5 (n = 20)
µm, respectively. Superfusion with 0.1 and 1 µmol/l adenosine did
not significantly alter afferent and efferent arteriolar diameters;
however, 10 µmol/l adenosine significantly reduced afferent and
efferent arteriolar diameters (
8.2 ± 0.8 and 5.7 ± 0.6%, respectively). The afferent and efferent arteriolar
vasoconstrictor responses to adenosine waned at a dose of 100 µmol/l,
such that diameters returned to values not significantly different from
control within 2 min. During adenosine A1 receptor blockade
with 8-noradamantan-3-yl-1,3-dipropylxanthine (KW-3902: 10 µmol/l),
10 and 100 µmol/l adenosine significantly increased afferent diameter
by, respectively, 8.1 ± 1.2 and 13.7 ± 1.3% (n = 14) and efferent arteriolar diameter by 6.4 ± 1.3 and 9.3 ± 1.2% (n = 8). The afferent and
efferent arteriolar vasodilatory responses to adenosine in the presence
of KW-3902 were significantly attenuated by addition of the adenosine
A2a receptor antagonist 1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF-17837: 15 µmol/l, n = 7 and 6, respectively). The addition of
KF-17837 alone significantly enhanced afferent (n = 15)
and efferent (n = 6) arteriolar vasoconstrictor
responses to 1, 10, and 100 µmol/l adenosine. These results indicate
the presence of adenosine A1 and A2a receptors
on afferent and efferent arterioles of juxtamedullary nephrons, such
that adenosine A2a receptor-mediated vasodilation partially
buffers adenosine-induced vasoconstriction in both pre- and
postglomerular segments of the renal microvasculature.
adenosine; afferent arterioles; efferent arterioles; KW-3902; KF-17837
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