Mechanism involved in bradykinin-induced efferent arteriole dilation

Abstract

Background. There is evidence that kinins play a role in the regulation of renal hemodynamics. The balance of vascular resistance in afferent and efferent arterioles (Af-Art and Ef-Art) is a crucial factor in controlling glomerular filtration. We have previously reported that bradykinin has a biphasic effect on the Af-Art and that dilation and constriction are due to cyclooxygenase products, not nitric oxide (NO). The present study was designed to examine (1) the direct effect of bradykinin on the Ef-Art and (2) the mechanisms that mediate bradykinin-induced Ef-Art dilation. Methods. Isolated Ef-Arts were microperfused retrograde while maintaining the Ef-Art pressure at 30 mm Hg. Isolated Ef-Arts were preconstricted with norepinephrine. Results. Perfusing the Ef-Art lumen with bradykinin caused dose-dependent vasodilation, increasing diameter from 6.9 ± 0.7 to 8.0 ± 0.8 (0.01 nmol/L), 8.3 ± 0.7* (0.1 nmol/L), 10.3 ± 0.7* (1 nmol/L) and 11.5 ± 0.8* μm (10 nmol/L; N = 8; *P < 0.05 vs. NE). Neither L-NAME nor indomethacin blocked the vasodilator effect of bradykinin; the diameter increased from 8.1 ± 0.9 to 12.9 ± 0.6 μm (10 nmol/L; P < 0.05 vs. control; N = 6) in the L-NAME-treated group and from 7.4 ± 0.9 to 11.0 ± 1.0 μm (10 nmol/L; P < 0.05 vs. control; N = 6) in the indomethacin-treated group. However, 25 μmol/L 17-ODYA, a cytochrome cP450 inhibitor, blocked the vasodilator effect of 10-8 mol/L bradykinin, leaving diameter unchanged (from 7.9 ± 0.8 to 7.7 ± 0.7 μm; N = 6). Finally, 0.1 μmol/L icatibant, a B2 receptor antagonist, completely blocked the vasodilation induced by bradykinin, and the diameter went from 7.8 ± 0.7 to 8.3 ± 0.8 3m (10 nmol/L). Conclusions. Bradykinin dilates Ef-Arts, but in contrast to Af-Arts its effect is not biphasic. The vasodilator effect of bradykinin in Ef-Arts via B2 receptors is mediated by cP450 metabolites (probably EETs), but not by NO or cyclooxygenase products.