From the Division of Hypertension and Vascular Research, Henry Ford
Hospital, Detroit, Mich.
Correspondence to Jeffrey L. Garvin, Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202.
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-Arg9]-bradykinin (10-9 and
10-8 mol/L), a B1 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 B2 receptor antagonist, blocked both the
vasodilation and vasoconstriction induced by bradykinin as well as the
vasoconstriction induced by [des-Arg9]-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 H2/thromboxane
A2 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 B2 receptors. The mechanisms
of vasodilation and vasoconstriction are due to
cyclooxygenase products, not nitric oxide.
© 1998 American Heart Association, Inc.
Scientific Contributions
Biphasic Effect of Bradykinin on Rabbit Afferent Arterioles
Key Words: prostaglandins • nitric oxide • renal blood flow • receptors • thromboxane
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