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.
Several investigators have shown that bradykinin increases renal blood
flow12–19; however, few have directly
investigated the effects of bradykinin on the afferent arteriole
without the confounding effects of the proximal and distal vasculature.
Edwards et al20 studied the effect of bradykinin
on afferent arterioles in vitro but found none. These studies focused
primarily on the effects of bradykinin added to the bath. Because the
results of Edwards et al20 clearly conflict with
the in vivo data, we investigated the effect of bradykinin on isolated
perfused afferent arterioles in the presence of flow.
In addition to the uncertainty regarding the action of bradykinin on
the afferent arteriole, the mechanisms by which it acts are also
unclear. There are at least two significant bradykinin receptors:
B1 and B2. A majority of
studies have shown that the effects of bradykinin are due to activation
of the B2 receptor.21 22 23 24 25 26
However, Lortie et al12 have shown that the
increase in renal blood flow induced by bradykinin is due to both
B1 and B2 receptors. In
addition, the second messenger cascades activated by these
receptors are also in question. There are data that support roles for
NO,13 prostaglandins and
NO,26 and P450–arachidonic acid
products.14 The explanation for these
disparate results is unclear; however, they may be due to differences
in experimental design.
Microdissection and cannulation of the afferent arteriole were
completed within 90 minutes at 8°C, after which the bath was
gradually warmed to 37°C for the rest of the experiment. Once the
temperature was stable, a 30-minute equilibration period was allowed
before any measurements were taken. Images of the afferent arterioles
were displayed at magnifications up to x1980 and recorded with a
video system. The diameter was measured with an image analysis
system.
Phenylephrine, L-NAME (an NO synthase
inhibitor), and indomethacin (a
cyclooxygenase inhibitor) were
purchased from Sigma Co. SQ29548, a
TXA2/PGH2 receptor
antagonist, was obtained from Biomol. Bradykinin and
[des-Arg9]-bradykinin were purchased from
Bachem Co.
Because bradykinin may be broken down over time when dissolved in BSA,
we tested kininogenase activity in several different preparations of
BSA. We found that standard BSA had the least kininogenase activity;
thus, we used standard BSA in all solutions throughout the experiments.
In addition, bradykinin was added to the perfusate immediately
before its use to avoid time-dependent breakdown. Measurements were
made 5 to 10 minutes later. Icatibant and
[des-Arg9]-bradykinin were prepared in the same
manner as bradykinin. Phenylephrine was used to
preconstrict the arterioles to approximately 50% of their initial
diameter. The range of concentrations required for this was 0.1 to
3 µmol/L.
Statistics
Because 10-9 to 10-8
mol/L bradykinin reduced luminal diameter in preconstricted afferent
arterioles, we next determined whether the latter concentration reduced
the diameter of nonpreconstricted afferent arterioles. For this,
10-8 mol/L bradykinin was added to the
perfusate of nonpreconstricted afferent arterioles. Basal
luminal diameter was 19.3±0.7 µm and did not change when
bradykinin was added (19.6±0.8 µm; n=3). Taken together, these
data indicate that bradykinin only constricts afferent arterioles when
vascular tone is present.
Because bradykinin only exerted its effects in preconstricted afferent
arterioles, in the remaining protocols all arterioles were
preconstricted to
Bradykinin may be released into the interstitium as well as the
vascular space; therefore, we next studied the effect of
10-12 to 10-8 mol/L
bradykinin in the bath. Bradykinin had no significant effect on
preconstricted afferent arterioles when added to the bath (Figure 2
Because bradykinin exerts most of its vascular actions through
B1 and B2 receptors, the
biphasic effect of bradykinin could be explained by activation of 2
receptor subtypes. We tested the ability of the
B2 receptor antagonist icatibant to
block the effects of bradykinin. First, 10-7
mol/L icatibant was added to the perfusate, and afferent
arterioles were preconstricted with phenylephrine.
Bradykinin was then added to the perfusate in increasing
concentrations from 10-12 to
10-8 mol/L. Icatibant blocked both the
vasodilation induced by low concentrations of bradykinin and the
vasoconstriction induced by high concentrations (Figure 3
To examine whether the B1 receptors are also
involved in the action of bradykinin, we first tested whether
[des-Arg9]-bradykinin, a
B1 receptor agonist, mimics the effect of
bradykinin. The addition of
[des-Arg9]-bradykinin
(10-9 mol/L) to the lumen reduced diameter from
9.7±1.1 to 7.0±1.1 µm, and 10-8 mol/L
reduced it further to 6.7±1.2 µm. Next, we tested whether the
B1 receptor agonist exerts its effect via the
B2 receptor. In the presence of
10-7 mol/L icatibant,
[des-Arg9]-bradykinin had no effect (Figure 4
Next, we examined the mechanism of bradykinin's actions. Because
bradykinin is known to stimulate NO release in other vascular beds,
resulting in vasodilation, we first studied the role of NO in mediating
bradykinin-induced dilation of afferent arterioles. Initially, luminal
diameter was 16.6±0.6 µm. After 10-4
mol/L of L-NAME, an inhibitor of NO synthesis, was added to
the perfusate, luminal diameter decreased to 12.8±1.3
µm. Afferent arterioles were then preconstricted, and the effect of
bradykinin was examined as before. Bradykinin dilated L-NAME–treated
afferent arterioles to the same extent as arterioles not treated with
L-NAME (Figure 5
Bradykinin is also known to stimulate the release of both vasodilator
and vasoconstrictor cyclooxygenase
products.14 29 30 Because NO did not appear
to be important in the dilation induced by bradykinin, we tested
whether prostaglandins mediate bradykinin-induced dilation
and/or constriction. Initially, luminal diameter was 18.7±1.1
µm. When indomethacin (5 µmol/L) was added to
the lumen and bath, diameter did not change. As shown in Figure 6
Because we found that indomethacin unmasked a
vasodilator effect of high doses of bradykinin, we next investigated
the mechanism involved. We postulated that the vasodilation produced by
high doses of bradykinin was mediated by NO. To test this,
indomethacin was added as before (to unmask the dilator
action of high doses of bradykinin), and then
10-4 mol/L L-NAME was added to the
perfusate. With 10-9 to
10-8 mol/L bradykinin, luminal diameter rose
from 6.2±0.7 to 10.7±0.6 µm (P<0.001) in the
untreated group but did not increase significantly in the
L-NAME–treated group (P>0.1). Thus, L-NAME prevented the
vasodilation induced by 10-9 and
10-8 mol/L bradykinin in
indomethacin-treated afferent arterioles (Figure 7
Finally, we investigated whether the cyclooxygenase
product(s) involved in bradykinin-induced vasoconstriction were
acting via the TXA2/PGH2
receptor by examining the ability of SQ29548, a
TXA2/PGH2 receptor
antagonist, to block vasoconstriction. Initially, luminal
diameter was 17.0±2.0 µm. Pretreatment of afferent arterioles
with SQ29548 did not alter basal diameter. Concentrations of bradykinin
from 10-12 to 10-10 mol/L
induced vasodilation, as seen in untreated preconstricted arterioles;
however, 10-9 and 10-8
mol/L bradykinin caused further dilation in the presence of SQ29548
rather than vasoconstriction (Figure 8
In the present study, we examined the direct action of
concentrations of bradykinin ranging from 10-12
to 10-8 mol/L on isolated microperfused afferent
arterioles of rabbits. We chose these concentrations because
concentrations of bradykinin reported in the literature range from
2x10-12 mol/L31 to
5x10-5 mol/L.32 When
bradykinin was added to the lumen, it dilated preconstricted arterioles
at concentrations ranging from 10-12 to
10-10 mol/L, whereas concentrations of
10-9 and 10-8 mol/L
induced vasoconstriction. Because 10-8 mol/L
induced vasoconstriction, we next examined whether it would do so
without the arterioles first being treated with low concentrations of
bradykinin. The decrease in diameter induced by
10-8 mol/L was similar in preconstricted
arterioles whether or not they were first treated with low
concentrations of bradykinin. Finally, we tested whether
10-8 mol/L bradykinin could constrict afferent
arterioles that had not been preconstricted with
phenylephrine. This concentration of bradykinin had no
effect on diameter in the absence of phenylephrine. These
data suggest that either bradykinin induces vasoconstriction only when
there is basal tone or else there is some synergism between bradykinin
and phenylephrine.
Our finding that luminal bradykinin has a biphasic effect on afferent
arteriole diameter indicates that it should also have a biphasic effect
on renal vascular resistance, since the afferent arteriole accounts for
a large portion of the latter
parameter.33 34 Previous reports of
the effects of bradykinin on renal blood flow have indicated only that
bradykinin induces vasodilation.12 13 16 17 19
However, Guimaraes et al35 did report that
lysylbradykinin has a temporal biphasic effect on renal vascular
resistance in vivo. The reason for the disparate results is unclear,
but it should be noted that in many of the aforementioned studies only
1 concentration of bradykinin was used13 18 19
and/or animals were pretreated with a
cyclooxygenase
inhibitor.13 14 18 19 Our data
indicate that if afferent arterioles are first treated with a
cyclooxygenase inhibitor, they only
dilate when challenged with bradykinin.
In our studies, when bradykinin was added to the lumen, it had a
biphasic effect on diameter in preconstricted vessels. These results
differ from those of Edwards et al.20 This is
undoubtedly due to differences in experimental design. In our
experiments, arterioles were exposed to flow and luminal bradykinin
(from 10-12 to 10-8
mol/L) after the vessels were preconstricted. In the study by Edwards
et al,20 there was no flow through the lumen of
the arterioles and only 0.1 µmol/L bradykinin was used. Edwards
et al reported that bradykinin did not alter arteriolar diameter when
added to vessels that were not preconstricted, or when added to the
lumen simultaneously with norepinephrine. The
former results are similar to ours; however, according to our data, the
latter protocol should have induced vasoconstriction. Two possible
explanations for the discrepancy are that (1) the reduction in diameter
induced by bradykinin, when added simultaneously with
norepinephrine, may not have been large enough to
distinguish from that of norepinephrine alone; or (2) the
differences may be due to the presence or absence of flow. There was no
luminal flow in the experiments of Edwards et al, but in our studies
there was. The response of the afferent arteriole to vasoactive agents
has been shown to be modified by flow.36
Because bradykinin may also be formed in the interstitial
space as well as the luminal space, we added bradykinin to the bath.
When this was done, bradykinin had no effect on preconstricted afferent
arterioles. This result was similar to that reported by Edwards et
al.20 While it is unclear why bradykinin alters
afferent arteriolar diameter when added to the lumen but not the bath,
possible explanations may be that (1) bradykinin acting via receptors
on smooth muscle cells induces constriction while receptors on
endothelial cells induce dilation, and the two effects
cancel each other; (2) bradykinin induces only very weak contractions
in the smooth muscle of arterioles and does not reach the
endothelium when added to the bath because of
degradation; or (3) bradykinin has no direct effect on vascular smooth
muscle of the afferent arteriole, and the receptors on the
endothelium are localized to the luminal membrane.
Most of the effects of bradykinin are mediated via
B1 and B2 receptors. In the
present study, we found that both the vasodilation and
vasoconstriction induced by bradykinin were mediated by the
B2 receptor. The bradykinin
B2 receptor is thought to mediate not only
endothelium-dependent vasodilation of canine carotid,
bovine or porcine coronary arteries and canine renal
arteries37 38 39 but also venoconstriction and
smooth muscle contraction.39 40 41 These results
are consistent with immunohistochemical
studies,42 which have shown that afferent
arterioles have numerous B2 receptors. Our
results indicate that the effects of B1 receptor
agonists may actually be mediated via the B2
receptor. However, concern about the selectivity of icatibant and
[des-Arg9]-bradykinin for the appropriate
receptors remains an issue. Consequently, we cannot completely
eliminate a role for the B1 receptor in
bradykinin's action.
The mechanisms by which bradykinin exerts its effects are unclear. In
this study, we found that blocking cyclooxygenase
with indomethacin abolished both bradykinin-induced
dilation and constriction of preconstricted afferent arterioles. These
data indicate that cyclooxygenase products are
responsible for most of the effects of bradykinin on the afferent
arteriole. We also found that the vasoconstriction induced by
bradykinin was blocked by a
PGH2/TXA2 receptor
antagonist, indicating that 1 or both of these constrictor
compounds is responsible for the reduction in arteriolar diameter
induced by 1 and 10 nmol/L bradykinin. Bradykinin also has been found
to stimulate the release of vasodilator prostaglandins from
cultured endothelial cells29 and
is known to stimulate phospholipase
A2,43 causing the release
of arachidonic acid and the subsequent synthesis of
cyclooxygenase or lipoxygenase
products.
If the ability of bradykinin to release prostaglandins is
blocked, we found that bradykinin-induced release of NO will dilate the
afferent arteriole. After indomethacin blocked the
vasoconstriction induced by high doses of bradykinin, vasodilation was
unmasked that could be blocked by an NO synthesis
inhibitor, L-NAME. In the absence of
indomethacin, pretreatment of arterioles with L-NAME
failed to affect the response of afferent arterioles to bradykinin.
Taken together, these data suggest that low concentrations of
bradykinin induce the release of vasodilator
cyclooxygenase products, whereas higher doses
release vasoconstrictor cyclooxygenase
products, probably PGH2 or
TXA2. Finally, cyclooxygenase
products mask the effect of NO release by bradykinin at
concentrations >10-9 mol/L on afferent
arterioles. Whereas bradykinin stimulates the production of
several classes of prostaglandins, tissue responsiveness to
a particular class of prostaglandin (ie, vasoconstrictor or
vasodilator) may determine whether the net response is constriction or
relaxation.
Our results are similar to those of Guimaraes et
al,35 Siragy et al,26 and
Quilley et al,14 who showed that the dilation
induced by bradykinin is mediated by prostaglandins. These
findings can also be reconciled with those of Lahera et
al,13 who have shown that the renal vasodilator
response to bradykinin is mediated by NO, since the dogs were first
treated with meclofenamate, a cyclooxygenase
inhibitor.
In conclusion, bradykinin has a biphasic effect on afferent arterioles.
Both dilation and constriction may be mediated by the bradykinin
B2 receptor. The mechanisms of vasodilation and
vasoconstriction are primarily due to
cyclooxygenase products, not NO.
Bradykinin-induced NO release dilates vessels if
cyclooxygenase is inhibited.
Received January 26, 1998;
first decision February 12, 1998;
accepted March 9, 1998.
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© 1998 American Heart Association, Inc.
Scientific Contributions
Biphasic Effect of Bradykinin on Rabbit Afferent Arterioles
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
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.
Key Words: prostaglandins • nitric oxide • renal blood flow • receptors • thromboxane
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
The kallikrein-kinin
system has been reported to play a role in the regulation of renal
hemodynamics and thereby in sodium and water excretion,
blood pressure, and renin release.1 2 3 4 5 6 7 8 Previous
studies have shown that kallikrein from the connecting tubule enters
the vascular space9 10 11 as well as the
interstitium,8 where it produces bradykinin.
Thus, both plasma bradykinin and interstitial bradykinin
may be significant regulators of afferent arteriole resistance.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Kidneys of young male New Zealand White rabbits (1.4 to 2.2 kg)
were removed and sliced longitudinally along the
corticomedullary axis. The slices were placed in
ice-cold minimum essential medium (MEM; Gibco Laboratories) containing
5% BSA (Intergen Co), and a single superficial afferent arteriole with
its glomerulus intact was dissected. This arteriole was transferred to
a perfusion chamber mounted on an inverted microscope and cannulated
with an array of glass pipettes as described
previously.27 28 The afferent arteriole was
perfused with oxygenated MEM containing 5% BSA, with
intraluminal pressure maintained at 60 mm Hg throughout the
experiment. Luminal flow was approximately 300 µL/min. The bath was
similar to the perfusate except that it contained 0.1% BSA and
was exchanged continuously. All studies were in accordance with the
guidelines of the Henry Ford Hospital Animal Care and Use
Committee.
Data are expressed as mean±SEM. Paired t tests were
used to examine whether the diameter at a given concentration was
different from the control value within each group.
Univariate repeated-measures ANOVA with the
Greenhouse-Geisser sphericity correction was used to test whether the
groups (treated versus nontreated) differed with respect to the rate of
change across the various periods. For this analysis,
P<0.05 was considered significant. If a significant or
borderline interaction effect was detected, Student's two-sample
t test (or Welch's test in the event of unequal variances)
was used to examine whether the change in diameter at a given
concentration differed between 2 groups. When more than 1 measurement
was made, Bonferroni's multiple comparison adjustment was used to
reduce the significance level.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Because in vivo studies have demonstrated that bradykinin
increases renal blood flow, we first examined whether it dilates
preconstricted arterioles. Afferent arterioles were preconstricted with
phenylephrine to approximately 50% of basal diameter,
after which increasing doses of bradykinin
(10-12 to 10-8 mol/L)
were added to the lumen. Bradykinin concentrations from
10-12 to 10-10 mol/L
increased luminal diameter in a dose-dependent manner as shown in
Figure 1
. Maximum dilation occurred at
10-10 mol/L, a concentration that increased
diameter from 9.9±1.0 to 14.3±1.2 µm. In contrast, higher
concentrations of bradykinin decreased luminal diameter, with
10-8 mol/L bradykinin reducing it from 14.3±1.2
to 9.7±1.2 µm (P<0.001; Figure 1). Time controls
showed no significant change in diameter. These data suggest that
bradykinin has a biphasic effect on preconstricted afferent
arterioles.
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Figure 1. Effect of luminal bradykinin on preconstricted
afferent arteriolar diameter. CON indicates diameter after constriction
with phenylephrine. *P<0.003 vs CON,
**P<0.001 vs BK 10-10 mol/L (n=8). 
50% of their basal diameter before the addition
of bradykinin. Next, we tested whether 10-8
mol/L bradykinin induces vasoconstriction without the confounding
dilator effects of the low doses of bradykinin. When
10-8 mol/L bradykinin was added to the lumen of
preconstricted arterioles, it decreased diameter from 10.7±0.9 to
8.3±0.8 µm (P<0.02). ). To demonstrate that these vessels
would respond to bradykinin, we then washed the bradykinin from the
bath and added it to the lumen. When added to the lumen, bradykinin
induced dilation.
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Figure 2. Effect of bradykinin added to the bath on
preconstricted afferent arteriolar diameter. B indicates added to the
bath; L, added to the lumen; and CON, diameter after constriction with
phenylephrine (n=5). *P<0.003 vs CON. ).
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Figure 3. Effect of bradykinin on preconstricted afferent
arteriolar diameter in the presence and absence of icatibant, a
B2 receptor antagonist. Icatibant, n=8;
vehicle, n=6. CON indicates diameter after constriction with
phenylephrine. *P<0.003 vs CON,
**P<0.001 vs BK 10-10 mol/L. ). These data suggest that the
vasodilator and vasoconstrictor actions of bradykinin may be mediated
by the bradykinin B2 receptor.
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Figure 4. Effect of [des-Arg9]-bradykinin, a
B1 receptor agonist, on the diameter of preconstricted
afferent arterioles in the presence of B2 receptor
antagonist icatibant. Icatibant, n=6; vehicle, n=7. CON
indicates diameter after constriction with phenylephrine.
*P<0.02 vs CON. ). Maximal dilation
occurred at 10-10 mol/L in both groups. Higher
concentrations of bradykinin caused similar vasoconstriction in both
groups. These data suggest that NO does not play a major role in the
response of the afferent arteriole to bradykinin.
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Figure 5. Effect of bradykinin on preconstricted afferent
arteriolar diameter in the presence and absence of L-NAME. Vehicle,
n=10; L-NAME, n=8. CON indicates diameter after constriction with
phenylephrine. With L-NAME: *P<0.001 vs
CON, **P<0.05 vs BK 10-10 mol/L. Without
L-NAME: *P<0.003 vs CON, **P<0.001 vs
BK 10-10 mol/L. , indomethacin blocked
both the dilation of preconstricted arterioles induced by low
concentrations of bradykinin and the constrictor action of high
concentrations. In fact, a vasodilator effect of
10-9 and 10-8 mol/L
bradykinin was now observed, with luminal diameter increasing from
6.2±0.7 to 10.7±0.6 µm at 10-8 mol/L
(P<0.001). These data suggest that
cyclooxygenase products mediate both
bradykinin-induced vasodilation and constriction.
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Figure 6. Effect of bradykinin on preconstricted afferent
arteriolar diameter in the presence of indomethacin.
CON indicates diameter after constriction with
phenylephrine (n=8). *P< 0.001 vs BK
10-10 mol/L. ). These data suggest that bradykinin
releases NO from rabbit afferent arterioles but only at concentrations
>10-9 mol/L.
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[in a new window]
Figure 7. Effect of L-NAME on bradykinin-induced
vasodilation in the presence of indomethacin. CON
indicates diameter after constriction with phenylephrine.
Indomethacin, n=8; indomethacin+L-NAME,
n=6. *P<0.001 vs BK 10-10 mol/L. ).
These data suggest that the vasoconstrictor effect of bradykinin takes
place via activation of the TXA2 and
PGH2 receptors.
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Figure 8. Effect of bradykinin on preconstricted afferent
arteriolar diameter in the presence of
TXA2/PGH2 receptor inhibitor
SQ29548. CON indicates diameter after constriction with
phenylephrine (n=5). *P<0.05 vs CON,
**P<0.03 vs BK 10-10 mol/L.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
In the present study, we investigated the direct effects of
bradykinin on the afferent arterioles, as well as the possible pathways
through which bradykinin works. We found that in the isolated
microperfused rabbit afferent arteriole, bradykinin has a biphasic
effect, inducing vasodilation at low concentrations and
vasoconstriction at higher concentrations. Both vasodilation and
vasoconstriction appear to be mediated by B2
receptors. Furthermore, our results suggest that bradykinin-induced
vasodilation and vasoconstriction are due to metabolites of the
cyclooxygenase pathway rather than NO.
Selected Abbreviations and Acronyms
B1, B2
=
bradykinin receptors 1 and 2
L-NAME
=
Nw-nitro-L-arginine methyl ester
NO
=
nitric oxide
PGH2
=
prostaglandin H2
SQ29548
=
thromboxane A2/prostaglandin
H2 receptor antagonist
TXA2
=
thromboxane A2
Acknowledgments
This work was supported by a grant from the National Institutes
of Health (HL-28982). Dr Yu was supported in part by a postdoctoral
fellowship from the National Kidney Foundation of Michigan. Dr Garvin
was supported in part by a research career development award
(HL-02891).
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
Barraclough MA, Mills IH. Effect of bradykinin on
renal function. Clin Sci. 1965;28:69–74.[Medline]
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