Biphasic Effect of Bradykinin on Rabbit Afferent Arterioles

Abstract

Abstract —Bradykinin plays an important role in the regulation of renal hemodynamics. However, there have been few studies of the effect of bradykinin on isolated afferent arterioles, vascular segments that are important for the regulation of renal blood flow and glomerular filtration rate. Our purpose was to study (1) the effects of bradykinin on isolated perfused rabbit afferent arterioles and (2) the mechanisms of actions. Afferent arterioles dissected from rabbits were perfused in vitro at 60 mm Hg. In afferent arterioles preconstricted with phenylephrine, 10 −12 to 10 −10 mol/L bradykinin increased luminal diameter from 9.0±1.0 to 14.3±1.2 μm ( P <0.003). In contrast, 10 −9 and 10 −8 mol/L bradykinin decreased luminal diameter to 10.8±1.4 and 9.7±1.2 μm, respectively ( P <0.001). Bradykinin added to the bath had no effect on preconstricted afferent arterioles. The addition of [des-Arg 9 ]-bradykinin (10 −9 and 10 −8 mol/L), a B 1 receptor agonist, to the lumen decreased diameter from 9.7±1.2 to 6.7±1.2 μm at 10 −8 mol/L ( P <0.002). Icatibant (Hoe 140), a B 2 receptor antagonist, blocked both the vasodilation and vasoconstriction induced by bradykinin as well as the vasoconstriction induced by [des-Arg 9 ]-bradykinin. L-NAME had no effect on bradykinin-induced dilation or constriction. Indomethacin blocked both the dilation induced by 10 −12 to 10 −10 mol/L bradykinin and the constriction induced by 10 −9 to 10 −8 mol/L bradykinin. In fact, in the presence of indomethacin, 10 −9 and 10 −8 mol/L bradykinin increased luminal diameter from 6.2±0.7 to 10.7±0.6 μm at 10 −8 mol/L ( P <0.001), which was attenuated by L-NAME. Finally, in the presence of SQ29548, a prostaglandin H 2 /thromboxane A 2 receptor antagonist, bradykinin caused dilation at all concentrations tested. In conclusion, bradykinin has a biphasic effect on afferent arterioles. Both dilation and constriction may be mediated by bradykinin B 2 receptors. The mechanisms of vasodilation and vasoconstriction are due to cyclooxygenase products, not nitric oxide.