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Endothelin-1-induced responses in isolated mouse vessels: the expression
and function of receptor types
Yingbi Zhou,1,2 Wessel P. Dirksen,1 Jay L. Zweier,2 and Muthu Periasamy1
1Department of Physiology and Cell Biology and 2Davis Heart and Lung Research Institute,
College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210
Submitted 9 December 2003; accepted in final form 7 April 2004
Zhou, Yingbi, Wessel P. Dirksen, Jay L. Zweier, and Muthu
Periasamy. Endothelin-1-induced responses in isolated mouse ves-
sels: the expression and function of receptor types. Am J Physiol
Heart Circ Physiol 287: H573–H578, 2004. First published April 8,
2004; 10.1152/ajpheart.01170.2003.—Mice have been increasingly
used as models for investigating cardiovascular diseases. However,
the responsiveness of mouse vasculature to endothelin (ET)-1 has not
been clearly established. The goal of this study was to determine the
role of ET receptors (ETA and ETB) in mouse vessels using isometric
force measurements. Results showed that in the abdominal aorta ET-1
induced a concentration-dependent contraction (EC50: 1.4 nM) with
maximum reaching 89.5 � 4.9% (10 nM) of that induced by 60 mM
K� [with nitric oxide synthase (NOS) inhibitor N�-nitro-L-arginine
methyl ester (L-NAME)]. However, in the thoracic aorta or the carotid
artery, ET-1 was poorly effective. RT-PCR revealed that in the
endothelium-denuded abdominal aorta, the PCR product for ETB
receptors was very low compared with ETA. Similarly in tissues
treated with L-NAME, the ETB receptor-specific agonist sarafotoxin
6c (S6c; 100 nM) induced only a minimal contraction (�5%). Mean-
while, the ETA antagonist BQ-123 (1 �M) completely inhibited the
maximum ET-1 (10 nM) contractile response. Furthermore, we found
that in the abdominal aorta that had not been treated with L-NAME,
ET-1-induced contraction significantly decreased. However, in such
specimens, S6c was unable to induce any relaxation on phenyleph-
rine-induced contraction. These results indicate that the role of ET
receptors differs considerably among mouse vessels. In the abdominal
aorta, ETA receptor mediates a potent vasoconstrictor response,
whereas ETB has, if any, only a minimal functional presence. Also,
our data suggest that ET-1 might involve a NOS-dependent vasodi-
lation in the abdominal aorta, which remains to be further defined.
endothelinA receptor; endothelinB receptor; vasoconstriction; nitric
oxide synthase; vasodilation
ENDOTHELINS (ETs: ET-1, ET-2, and ET-3) are a family of
regulatory peptides that have long-lasting vasoconstrictor and
pressor effects. Among them, ET-1 is the most active form
produced in the endothelial cells that plays an important role in
regulating cardiovascular function (14, 26). To date, two major
types of receptors, designated as ETA and ETB, have been
found to be responsible for the biological effects induced by
the endogenous ETs. Both ETA and ETB receptors belong to
the family of seven transmembrane G protein-coupled recep-
tors. However, each receptor type has distinctive ligand-bind-
ing properties and biological functions (13, 14).
In blood vessels, ETA receptors are mainly located in the
smooth muscle cells, and its activation by ET-1 leads to
vasoconstriction (13, 14). In contrast, ETB receptors exist both
in the smooth muscle and in the endothelial cells (13, 14).
While ETB receptors present in the smooth muscle mediate
vasoconstriction (13, 14, 24), those in the endothelial cell cause
vasodilation via the release of endothelium-dependent relaxing
factors, such as nitric oxide (NO) (12, 17, 23). However, it has
been recently found that part of the depressor effect of ETB
receptor may be related to the clearance of ET-1 in the plasma
(3, 5). In addition, ETA receptor has also been suggested to be
functional in the endothelial cells (11, 18, 19). Thus the
regulation of vascular tone by ET receptors appears to involve
a complicated mechanism that has yet to be fully understood.
Recently, genetically altered mice have been extensively
used to study ET-1-mediated signaling in the regulation of
cardiovascular function. Major mouse vessels from different
vascular beds, such as the aorta and the carotid artery, have
been the common targets for the pathological interventions to
study the pathogenesis of cardiovascular diseases (1, 16). On
the other hand, the responsiveness of these mouse vessels to
ET-1 has not been clearly established. For example, in the
thoracic aorta, ET-1 has been found to induce little contractile
response (20). Therefore, there is a pressing need to determine
whether ET receptors mediate the vasoconstrictor response
differently among mouse vessels. In addition, ETB receptors
have been proposed to mediate a NO-dependent vasodilation in
the mouse thoracic aorta (15). However, a previous study has
demonstrated that in the mouse thoracic aorta, ET-1, which
exhibits little vasoconstrictor effect, still elicits a contraction
rather than a relaxation in the presence of an intact endothelium
(20). Thus the role of ETB receptors in endothelial NO release
also needs to be further elucidated in mouse vessels.
Therefore, this study was designed to critically evaluate the
ET-1-induced responses in major mouse vessels, including the
thoracic aorta, the abdominal aorta, and the carotid artery,
employing isometric force measurements. We found that
among vessels studied, the mouse abdominal aorta exhibits a
potent vasoconstrictor response to ET-1. Then, the function of
ETA and ETB receptors in the abdominal aorta was further
determined with RT-PCR and receptor-specific agonist or an-
tagonist.
MATERIALS AND METHODS
Solution and chemicals. The ionic composition of physiological
saline solution (PSS) was as follows (in mM): 123 NaCl, 4.7 KCl,
15.5 NaHCO3, 1.2 KH2PO4, 1.2 MgCl2, 1.25 CaCl2, and 11.5 D-
glucose. The 60 mM K�-PSS (K�) was prepared by replacing an
equal molar of NaCl with KCl. Chemicals such as ET-1, the ETB
Address for reprint requests and other correspondence: M. Periasamy, Dept.
of Physiology and Cell Biology, The Ohio State Univ. College of Medicine,
304 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210 (E-mail:
periasamy.1@osu.edu).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Am J Physiol Heart Circ Physiol 287: H573–H578, 2004.
First published April 8, 2004; 10.1152/ajpheart.01170.2003.
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agonist sarafotoxin 6c (S6c), ACh, phenylephrine (PE), the ETA
antagonist BQ-123, and N�-nitro-L-arginine methyl ester (L-NAME)
were purchased from Sigma (St. Louis, MO). Other chemicals were
also of the highest grade commercially available.
Animals and tissue preparation. Male C57/BL6J mice (8–12 wk)
purchased from Jackson Laboratory were euthanized by 95% CO2
inhalation, in accordance with animal use protocol of the Animal
Research Ethics Committee of The Ohio State University. Tissues
including the thoracic aorta, the abdominal aorta, the carotid artery,
and the trachea were excised rapidly and placed in ice-cold PSS. The
fat and the adventitia were mechanically removed under a binocular
microscope. Then, the vessels and the trachea were cut transversely
into �1.0-mm-wide rings. These procedures were performed at room
temperature.
Isometric force measurement. The method of isometric force mea-
surement is described elsewhere (27, 28). Briefly, the vascular or
tracheal ring was mounted onto two tungsten wires in a 37°C water-
circulating tissue bath filled with PSS, by passing the tungsten wires
through the lumen of tissue specimen. One of the wires was fixed, and
the other was connected to a force transducer (AE 801, Horten,
Norway).During the equilibration period, tissues were stimulated
with 60 mM K� every 15 min (5 times), and the resting tension was
increased in a stepwise manner. After the equilibration, the resting
tension was adjusted to �300 mg for the vascular rings, and 200 mg
for tracheal specimens, at which the maximal 60 mM K� response
was obtained.
Detection of ET receptor mRNAs in mouse abdominal aorta. The
tissues were prepared as described above with the exception that they
were not cut into rings. Vessels were cut open, and then the endothe-
lial cells were removed by wiping with a cotton swab under a
binocular microscope followed by washes until no trace of endothe-
lium was detected. RNA preparation and RT-PCR were performed
according to the manufacturer’s manual using an Absolutely RNA
RT-PCR Miniprep Kit (Stratagen, La Jolla, CA). Primers for ET
receptors were as follows: 5�-ATGGTGGGGAACGCAACTC-
TACTA-3� (PCR sense) and 5�-GACGCTGTTTGAGGTGCTCAC-
TAA-3� (RT and PCR antisense) for the ETA receptor and 5�-GGGTT
CCAAAATGGACAGTAG-3� (PCR sense) and 5�-CTCCAAG-
GACTGCTTTTCCTCAAA-3� (RT and PCR antisense) for the ETB
receptor. RT reaction was performed using 200 ng of total RNA in a
volume of 20 �l. The protocols for PCR were as follows: 94°C for
30 s, 60°C for 60 s, and 72°C for 60 s (28–30 cycles as indicated). The
expected sizes of PCR products were 622 bp for ETA and 608 bp for
ETB. To determine the specificity of RT-PCR reactions, the PCR
products were digested with 10 units of BamHI (NEB, Beverly, MA)
according to the manufacturer’s instruction. This treatment yields
fragments of 310 and 312 bp for ETA and 215 and 393 bp for ETB
according to the mouse cDNA sequences. The PCR products were
separated with 2% agarose gel and visualized with ethidium bromide
staining.
Experimental protocols. The physiological studies were conducted
in blood vessels with intact endothelium at 37°C. In all experiments,
an agonist was used only once in each specimen. Unless otherwise
indicated, the agonist was administered 15 min after the final 60 mM
K� contraction had been relaxed with PSS. The force development
caused by an agonist was expressed as a percentage of that obtained
with 60 mM K�, assuming the value in the PSS (5.9 mM K�) and 60
mM K� to be 0 and 100%, respectively. In certain experiments, 1 mM
of the NO synthase (NOS) inhibitor L-NAME was added 5 min before
an agonist was applied to eliminate the endothelial NO (27, 28). The
effect of an agent to induce endothelium-dependent relaxation was
examined on PE-induced contractions in vessels that had not been
treated with L-NAME. The extent of the force change was expressed
as a decrease or increase of force in a percentage of that induced by
60 mM K�.
Data analysis. The EC50 value, a concentration at which 50% of
maximum response was obtained, was determined from the concen-
tration-response curves fitted to a four-parameter logistic model (7).
Data are expressed as means � SE. Student’s t-test was used to
determine the statistical significance. P � 0.05 was considered to
indicate statistical significance.
RESULTS
ET-1-induced contractile response in mouse vessels. The
effects of ET-1 on major mouse vessels have not been explored
in detail. To determine how different mouse vessels respond to
ET-1, isolated vessels including the abdominal aorta, the tho-
racic aorta, and the carotid artery were studied using isometric
force measurements. Because ET-1 might mediate a concom-
itant endothelial NO release (14, 17, 23), the contractile re-
sponse was evaluated in the presence of 1 mM L-NAME, which
has been previously shown to abolish the endothelium-depen-
dent relaxation induced by ACh in major mouse blood vessels
(6, 28).
In the abdominal aorta, 60 mM K� induced a contraction of
341 � 15 mg. As shown in Fig. 1A, in response to 0.1, 1, 10,
and 100 nM ET-1 stimulation, the mouse abdominal aorta
developed a contraction of 0 � 0, 36.5 � 3.4, 89.5 � 4.9, or
88.6 � 4.1%, respectively, compared with that of 60 mM K�.
Accordingly, the EC50 value and the maximum response con-
centration were obtained at 1.4 nM and 10 nM, respectively. In
addition, as demonstrated in Fig. 1B, the maximum contractile
response induced by 10 nM ET-1 showed a sustained property
similar to those seen in other species (24).
In the thoracic aorta and the carotid artery, 60 mM K�
caused a contraction of 420 � 18 or 178 � 21 mg, respec-
tively. After 10 nM ET-1 stimulation, a sustained contraction
also developed (Fig. 2). However, the extent of contraction was
Fig. 1. Endothelin (ET)-1-induced contractile response in the mouse abdom-
inal aorta. A: concentration-response curves of ET-1 in mouse abdominal aorta.
ET-1 was used only once in each specimen and was administered 5 min after
the application of 1 mM N�-nitro-L-arginine methyl ester (L-NAME). The
force development was expressed as a percentage compared with that induced
by 60 mM K�. The values are expressed as means � SE (n � 4–5). B:
representative recordings showing the maximum contractile response induced
by 10 nM ET-1 in the presence of L-NAME.
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only 7.8 � 2.7 and 8.3 � 4.2% compared with that of 60 mM
K� in the thoracic aorta and the carotid artery, respectively. In
addition, ET-1-induced responses in these two vessels were not
increased even when higher concentrations were used (100
nM, data not shown). These results indicate that ET-1-induced
contractile responses vary among the major mouse vessels.
Expression of ET receptor mRNAs in mouse vessels. The
above results demonstrate that ET receptors mediate a potent con-
tractile response in the mouse abdominal aorta. To determine the
receptor type(s) involved, ET receptor mRNAs were first exam-
ined with RT-PCR in the endothelium-denuded specimens. From
28 to 30 thermal cycles, PCR products of expected sizes for ETA
(622 bp) and ETB (608 bp) receptors were detected. However, the
band density of the PCR product for the ETB receptor was very
low compared with the ETA receptor (lanes 1 and 2, Fig. 3, 30
cycles). To further confirm that the PCR products of expected
sizes were amplified from respective mRNAs, enzymatic diges-
tion with BamHI was performed. As shown in Fig. 3, the products
for the ETA receptor turned into a single band of �310 bp (lane
3), while those for the ETB receptor appeared as bands of 215 and
393 bp (lane 4), which is well consistent with mouse cDNA
sequences (310 and 312 bp for ETA; 215 and 393 bp for ETB).
Effect of ET receptor-specific agonist or antagonist. An
explanation for the low abundance of ETB PCR products could
be that ETB is not a major receptor type in the smooth muscle
cells of mouse abdominal aorta. To test this hypothesis, we
examined the effects of the ETB receptor-specific agonist S6c
and the ETA receptor-specific antagonist BQ-123. As shown in
Fig. 4A, top, in the presence of 1 mM L-NAME, S6c (100 nM)
induced only a contraction of 4.8 � 0.9% (n � 3) compared
with that of 60 mM K�. However, in the mouse trachea, in
which ETB receptor has been previously found to have a
significant functional presence (10), 100 nM S6c caused a
contraction of 65% (Fig. 4A, bottom). In addition, the ETA-
specific antagonist BQ-123 (1 �M) completely antagonized the
maximum contractile response (in the presence of 1 mM
L-NAME) induced by 10 nM ET-1. These results together
point to the conclusion that ETA receptors account for most of
Fig. 3. Detection of ET receptor mRNAs with RT-PCR in the endothelium-
denuded mouse abdominal aorta. Lanes 1 and 2: the level of PCR product
amplified (30 cycles) from mRNA of ETA (622 bp, lane 1) or ETB receptor (608
bp, lane 2). Lanes 3 and 4: an enzymatic analysis of PCR products (30 cycles) for
ETA (lane 3) and for ETB (lane 4) receptors with BamHI, which was expected to
produce fragments of 310 and 312 bp andthose of 215 and 393 bp, respectively.
M, 100-bp ladder size makers (top to bottom: 1,000–100 bp).
Fig. 2. Representative traces showing the maximum contractile response
induced by 10 nM ET-1 in the thoracic aorta (A) and in the carotid artery (B)
in the presence of 1 mM L-NAME.
Fig. 4. Effect of ET receptor type-specific agonist or antagonist in the mouse
abdominal aorta. A: representative recordings demonstrating the contractile
responses induced by the ETB receptor-specific agonist sarafotoxin 6c (S6c) in
the mouse abdominal aorta (top) and the trachea (bottom). B: representative
trace (from 3 identical experiments) showing the effect of ETA receptor
antagonist BQ-123 on ET-1-induced contractile response.
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ET-1-induced contractile response in the mouse abdominal
aorta.
Effect of ET-1 and S6c on mouse vessels with intact NOS
activity. ET-1 has been proposed to activate a concomitant endo-
thelial NO release, which can compromise part of its vasocon-
strictor effects (14, 14, 23). To test this in mice, ET-1-induced
responses in vessels with normal NOS activity were examined. As
shown in Fig. 5A, when L-NAME was omitted from the medium
the contraction induced by 1, 10, and 100 nM ET-1 (6.1 � 2.5,
26.4 � 3.8, or 67.1 � 5.3%, respectively) was significantly less
than that in the presence of L-NAME. However, in the thoracic
aorta and the carotid artery, the responses (8.2 � 3.6 and 7.3 �
2.7%, respectively) caused by 10 nM ET-1 were similar to those
in the presence of L-NAME. These results suggest that the NOS
activity may have a negative effect on ET-1-induced vasocon-
strictor response in certain mouse vessel types, such as the
abdominal aorta.
To further determine whether the decreased ET-1 response was
due to an ETB receptor-mediated endothelial NO-dependent re-
laxation, the effects of S6c on PE-induced contractions were
examined. As shown in Fig. 6, 100 nM S6c did not cause any
relaxation in abdominal aorta precontracted with either 0.3 or 1
�M PE. In contrast, the subsequent application of 10 �M ACh
produced a complete relaxation. Therefore, we propose that ETB
receptor may not be a major player in mediating endothelium-
dependent relaxation in the mouse abdominal aorta.
DISCUSSION
The goal of this study was to determine the function of ET
receptors in major mouse vessels. For this purpose, ET-1-
induced responses in different mouse vessels were examined
with isometric force measurements. Because ET receptors have
been proposed to mediate vasoconstriction as well as endothe-
lium-dependent vasodilation, ET-1-induced response in mouse
vessels was examined in the presence and absence of L-NAME,
a NOS inhibitor that is able to abolish ACh-induced relaxation
in major mouse vessels (6, 28). To further determine the
function of each ET receptor type, the expression of mRNA
and the effect of ET receptor-specific agonist or antagonist
were also examined in vessels that might have a potent re-
sponse to ET-1.
An important finding of this study is that ET-1 induces a
potent vasoconstrictor response in the mouse abdominal aorta.
As demonstrated by the concentration-response curve obtained
with the presence of NOS inhibitor L-NAME, ET-1-induced
contractile response in the mouse abdominal aorta is as potent
as those in human vessels, such as saphenous vein graft (12).
Thus it is clear that ET receptors play a significant role in
mediating the vasoconstriction in mice. However, ET-1-in-
duced responses are not uniform among major mouse vessels.
Fig. 5. Effect of nitric oxide synthase activity on ET-1-induced response. A:
summary of the contractile responses induced by different concentrations of
ET-1 in the abdominal aorta in the presence (open bars) and in the absence
(hatched bars) of 1 mM L-NAME (n � 4–5). B: summary of contractile
responses induced by 10 nM ET-1 in the presence (open bars) and in the
absence (hatched bars) of 1 mM L-NAME (n � 3–4) in the thoracic aorta (TA)
and the carotid artery (CA). The force development was expressed as a
percentage compared with that induced by 60 mM K�. The values are
expressed as means � SE. * P � 0.05.
Fig. 6. Representative recordings illustrating the effect of ETB receptor ago-
nist S6c (100 nM) on 0.3 �M (A) and 1 �M (B) phenylephrine (PE)-
precontracted mouse abdominal aorta. Top panels in A and B are controls.
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In the thoracic aorta, we found that 10 nM ET-1 only induced
a contraction of 7.8% compared with that of 60 mM K�,
similar to the results previously reported on the endothelium-
denuded tissue specimens (20). In addition, we found that the
carotid artery, a peripheral mouse vessel, is also poorly respon-
sive to ET-1 (8.3% as a percentage of that induced by 60 mM
K�). These results may suggest that the vasoconstrictor role of
ET receptors varies considerably among different mouse ves-
sels.
The above results prompt us to determine the ET receptor
type(s) mediating the contractile response in the abdominal
aorta. As shown by RT-PCR amplification, mRNAs of both ET
receptors are expressed in the endothelium-denuded speci-
mens. Interestingly, the PCR product for ETB was in very low
abundance (Fig. 3). We suspect that ETB receptors may not
have a major role in ET-1-induced contraction. However, the
RT-PCR reactions were performed using different primers. In
addition, there is a possibility of endothelial contamination.
Therefore, the functional involvement of receptor types was
further determined with a receptor-specific agonist or antago-
nist. As shown in Fig. 4A, the ETB receptor-specific agonist
S6c (100 nM) induced only a minimal contractile response in
the presence of L-NAME. However, the specific ETA antago-
nist BQ-123 (1 �M) completely antagonized the maximum
contractile response induced by 10 nM ET-1 (Fig. 4B). These
results altogether indicate that ETA, but not ETB, is the pre-
dominant vasoconstrictor ET receptor in the mouse abdominal
aorta, which concurs with reports on several rat as well as
human vessels (5, 8, 12, 21, 22, 25).
Also of interest is our finding that ET-1-induced contraction
in the abdominal aorta was significantly decreased when L-
NAME was omitted from the medium (Fig. 5A). This may
suggest an existence of NOS-dependent vasodilation that an-
tagonized part of the vasoconstrictor effect of ET-1. However,
in the thoracic aorta and the carotid artery, which exhibited a
minimal contractile response to ET-1, the effect of this NOS-
dependent vasodilation is not detectable (Fig. 5B), suggesting
that the basal NO release may not significantly modify the
contractility of isolated mouse vessels. In addition, we have
recently found that the response of mouse vessels (including
the abdominal aorta) to ANG II was not affected by L-NAME
(28). Therefore, the NOS-dependent vasodilation might be
specifically elicited by ET-1 stimulation, consistent with the
endothelial NO-releasing effects of ET-1 as generally proposed
(14, 17, 23). However, we were unable to remove the endo-
thelial cells in the mouse vascular rings efficiently to reach a
conclusion that the NOS-dependent vasodilation was origi-
nated from the endothelium.
In contrast to ET-1, the ETB receptor-specific agonist S6c,
which has only a minimal vasoconstrictor effect on the mouse
abdominal aorta, was unable to cause a vasodilating response
in tissue with intact endothelial function (Fig. 6). This may
suggest that ETB receptor does not mediate a significant extent
of endothelium-dependent relaxation in the abdominal aorta.
Thus the divergent effects of ET-1 in the abdominal aorta
might have been mediated by ETA receptor, whichseems
contradictory to the generally proposed role of ETB receptor in
the endothelium. However, it must be noted that ETA receptor
has been found to exist in the endothelial cells of certain vessel
types (11, 18). Also, the ETA receptor has been demonstrated
to mediate the Ca2� homeostasis in endothelial cells of porcine
aortic valves in situ (19). Thus ETA receptors could also
mediate the endothelial NO release, considering that the endo-
thelial NOS is a Ca2�-calmodulin-activated enzyme (9). How-
ever, we were unable to document an ETA receptor-mediated
relaxation. In addition, other unclassified ET receptors (non-A
and non-B receptors) might also exist (2). Therefore, the exact
mechanism for the NOS-dependent vasodilation that compro-
mised ET-1-induced contractile response in mouse abdominal
aorta requires further investigation.
The above results suggest that the ETB receptor may not be
significantly involved in mediating vasoconstriction or endo-
thelium-dependent vasodilation in the mouse abdominal aorta.
However, ETB receptors have been found to mediate the
vasoconstriction in certain mouse vessels. For example, both
ETA and ETB receptors have been found to mediate contraction
in the perfused renal or mesenteric arteries (4). Thus the
involvement of ET receptor types in vasoconstrictor response
also appears to differ depending on the location of a vessel. On
the other hand, there has been little direct evidence to indicate
that ETB receptor mediates endothelium-dependent relaxation
in mice, as those observed on porcine coronary and pulmonary
arteries (17, 23). We noted that the ETB receptor S6c had been
reported to produce a concentration-dependent relaxation in the
mouse thoracic aorta (15). However, we were unable to obtain
such a response using a similar experimental protocol (data not
shown). Instead, we found that ET-1 induced a subtle contrac-
tion with or without L-NAME (Fig. 5B), which is similar to a
report performed on specimens with or without endothelium
(20). As a result, the role of ETB receptor in mediating
endothelium-dependent relaxation in mice has yet to be further
elucidated.
In summary, in this study we examined ET-1-induced re-
sponses in isolated mouse vessels using isometric force mea-
surements. Our data demonstrate that the role of ET receptors
varies considerably among different mouse vessels. In the
abdominal aorta, ETA receptor mediates a potent vasoconstric-
tor response, while ETB has, if any, a minimal functional
presence. In addition, in the abdominal aorta, ET-1 might also
involve a NOS-dependent vasodilation, which remains to be
further defined.
ACKNOWLEDGMENTS
We thank M. Bonar for critical reading of the manuscript.
GRANTS
This work was supported by National Heart, Lung, and Blood Institute
(NHLBI) Grant HL-38355 to M. Periasamy and NHLBI Grants HL-63744,
HL-65608, and HL-38324 to J. L. Zweier. Y. Zhou is a recipient of an
American Heart Association (Ohio Valley) Postdoctoral Fellowship grant.
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H578 ENDOTHELIN-1 RESPONSES IN MOUSE VESSELS
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