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Departments of 1 Physiology and 2 Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112
The relative roles of ANG II and bradykinin (BK) in the
regulation of renal medullary circulation have remained unclear. We compared the contributions of ANG II and BK to the renal medullary blood flow (MBF) responses to angiotensin-converting enzyme (ACE) inhibition (enalaprilat, 33 µg · kg
1 · min
1)
in dogs maintained on a normal-salt diet (0.63%, 3 days,
n = 14;
group
1) with those fed a low-salt diet
(0.01%, 5 days, n = 14;
group
2), which upregulates both the
kallikrein-kinin and the renin-angiotensin systems. MBF responses to
ACE inhibition were evaluated either before
(n = 7) or after
(n = 7) treatment with the BK
B2 receptor blocker icatibant
(100-300 µg) in both groups. Laser-Doppler needle flow probes
were used to determine relative changes in MBF and cortical blood flow
(CBF). ACE inhibition increased MBF (group
1, 33 ± 9%,
P
0.01;
group
2, 24 ± 9%,
P
0.005) as well as CBF
(group 1, 23 ± 2%, P
0.006;
group
2, 28 ± 10%,
P
0.05). These responses were
prevented by prior blockade of B2
receptors in group
2, but not in
group
1. These data indicate that under
normal sodium intake, increases in MBF and CBF caused by ACE inhibition
are primarily due to reduced intrarenal ANG II levels. In contrast, the
renal vasodilatory responses to ACE inhibition in dogs on low salt
intake were markedly dependent on the activation of BK
B2 receptors.
laser-Doppler flowmetry; icatibant; bradykinin B2 receptors
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