Kinin influences on renal regional blood flow responses to angiotensin-converting enzyme inhibition in dogs

Abstract

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 micrograms . 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 micergrams) 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.