BIPHASIC EFFECT OF BRADYKININ ON RABBIT AFFERENT ARTERIOLES

Bradykinin plays an important role in the regulation of renal hemodyna mics. 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 p erfused rabbit afferent arterioles and (2) the mechanisms of actions. Afferent arterioles dissected from rabbits were perfused in vitro at 6 0 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 mu m (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 mu m, respectively (P<0.001). Bradykinin added to the bath had no effect on preconstricted afferent arterioles. The addition of [des-Arg(9)]-b radykinin (10(-9) and 10(-8) mol/L), a B-1 receptor agonist, to the lu men decreased diameter from 9.7+/-1.2 to 6.7+/-1.2 mu m at 10(-8) mol/ L (P<0.002). Icatibant (Hoe 140), a B-2 receptor antagonist, blocked b oth the vasodilation and vasoconstriction induced by bradykinin as wel l as the vasoconstriction induced by [des-Arg(9)] -bradykinin. L-NAME had no effect on bradykinin-induced dilation or constriction. Indometh acin blocked both the dilation induced by 10(-12) to 10(-10) mol/L bra dykinin and the constriction induced by 10(-9) to 10(-8) mol/L bradyki nin. 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 mu m at 10-8 mol/L (P<0.001), which was attenuated by L-NAME. Finally, i n the presence of SQ29548, a prostaglandin H-2/thromboxane A(2) recept or antagonist, bradykinin caused dilation at all concentrations tested . In conclusion, bradykinin has a biphasic effect on afferent arteriol es. Both dilation and constriction may be mediated by bradykinin B-2 r eceptors. The mechanisms of vasodilation and vasoconstriction are due to cyclooxygenase products, not nitric oxide.