Difference in Endothelium-Derived Hyperpolarizing
Factor–Mediated Hyperpolarization and Nitric Oxide
Release Between Human Internal Mammary Artery
and Saphenous Vein
Zhi-Gang Liu, MD; Zhi-Dong Ge, MD; Guo-Wei He, MD, PhD
Downloaded from http://circ.ahajournals.org/ by guest on October 1, 2016
Background—The greater nitric oxide (NO) release that occurs in the internal mammary artery (IMA) when compared
with the saphenous vein (SV) has been suggested by more endothelium-dependent relaxation in the IMA or measured
by bioassay; however, no direct measurement of NO- or endothelium-derived hyperpolarizing factor (EDHF)–mediated
hyperpolarization has been reported. The present study measured such hyperpolarization, as well as NO release, in
these vessels.
Methods and Results—IMA (n⫽46) and SV (n⫽61) segments taken from patients undergoing coronary surgery were
studied in the organ chamber. Hyperpolarization (by intracellular glass microelectrode) and NO release (by NO-sensitive
electrode) in response to acetylcholine and bradykinin, with and without incubation with NG-nitro-L-arginine,
indomethacin, and oxyhemoglobin, were measured. The resting membrane potential of the smooth muscle cells from the
IMA (58⫾0.8 mV; n⫽15) was higher than that in those from the SV (⫺62⫾0.9 mV; n⫽23; P⫽0.0001). The
EDHF-mediated hyperpolarization induced by acetylcholine (10⫺5 mol/L: ⫺9.4⫾1.5 mV in IMA, n⫽10, versus
⫺4.5⫾1.0 mV in SV, n⫽17; P⬍0.01) and bradykinin (10⫺7 mol/L: ⫺10.9⫾1.5 mV in IMA, n⫽8, versus ⫺5.1⫾0.5
mV in SV, n⫽8; P⬍0.01) and the basal release of NO (16.8⫾1.6 nmol/L in IMA, n⫽13, versus 9.9⫾2.8 nmol/L in SV,
n⫽13; P⬍0.001) were significantly greater in the IMA than in the SV. The duration of acetylcholine- and
bradykinin-induced NO release was longer in the IMA than in the SV.
Conclusions—The basal release of NO and EDHF-mediated hyperpolarization were significantly greater in the IMA than
in the SV. In addition, the duration of the stimulated release of NO was longer in the IMA than in the SV. These
differences may contribute to the superior long-term patency of IMA grafts. (Circulation. 2000;102[suppl
III]:III-296-III-301.)
Key Words: endothelium-derived factors 䡲 nitric oxide 䡲 arteries 䡲 veins 䡲 electrophysiology
T
he long-term benefit of myocardial revascularization
depends largely on the long-term patency of bypass
grafts. It is widely accepted that the long-term patency of an
internal mammary artery (IMA) graft is superior to that of a
saphenous vein (SV) graft.1,2 Clinical data show that at 10
years postoperatively, left IMA grafts placed in the left
anterior descending branch of the coronary artery have a
patency rate of 85% to 95%.3,4 In contrast, only 38% to 45%
of aortocoronary SV grafts remain open.2 Most importantly,
10-year survival in patients who have received a left IMA to
left anterior descending coronary artery graft is ⬇85%; it is
only 75% in those who receive SV grafts.3,4 Although
pathological studies revealed that the main reason for prolonged IMA graft patency is freedom from atherosclerosis in
the conduit, which may be attributed to histological features
of the IMA,1,5 the primary causes contributing to the different
patency rates between arterial and venous grafts are not fully
understood.
The endothelium plays a pivotal role in the regulation of
vascular tone and homeostasis.6,7 Apparently, the endothelial
function of the coronary bypass grafts is crucial to long-term
graft patency. In response to a variety of stimuli, the endothelial cells generate the following 3 major endotheliumderived relaxing factors: nitric oxide (NO), prostacyclin
(PGI2), and endothelium-derived hyperpolarizing factor
(EDHF).7 Of these factors, NO and PGI2 have attracted major
attention. This is partially related to the fact that the chemical
identification of EDHF has not been finalized, despite recent
studies suggesting epoxyeicosatrynoic acids, K⫹, or other
substances as candidates.8
A great amount of information concerning the physiological effects and biosynthesis of NO and PGI2 has been
From the Cardiovascular Research Laboratory, Grantham Hospital, University of Hong Kong, Hong Kong, China (Z.-G.L., Z-D.G., G-W.H.);
Cardiovascular Research, Starr Academic Center for Cardiac Surgery, St Vincent Hospital, Portland, Ore (G.-W.H.); and Xiamen University Medical
College, China (G.-W.H.).
Correspondence to Professor Guo-Wei He, MD, PhD, Chair of Cardiothoracic Surgery, University of Hong Kong, Grantham Hospital, 125 Wong Chuk
Hang Road, Aberdeen, Hong Kong. E-mail gwhe@hkucc.hku.hk
© 2000 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
III-296
Liu et al
acquired. Experimental studies have demonstrated that the
IMA has greater basal and stimulated production of PGI2 than
does the SV9 and that endothelium-dependent relaxation is
significantly greater in the IMA than in the SV.10 Further, NO
release from the IMA and SV was measured by a group from
the Mayo Clinic.11,12 However, direct quantitative measurement of the NO released from the IMA and SV has never
been reported. In addition, the role of EDHF in human
coronary bypass grafts has not been well studied, although we
have reported the effect of EDHF in human SVs.13
Therefore, the present study was designed to measure NO
release from the endothelium of the IMA and SV directly and
to examine the role of EDHF-mediated hyperpolarization,
with an emphasis on the different regulating effects of NO
and EDHF in the arterial and venous coronary bypass grafts.
Methods
Vessel Preparation
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Approval to use discarded tissue was obtained from the Ethics
Committee of Grantham Hospital, University of Hong Kong. The
discarded IMA (n⫽46) and SV (n⫽61) segments were obtained from
patients undergoing coronary artery bypass grafting; they were
immediately placed in a container with oxygenated physiological
solution (Krebs) that was maintained at 4°C and transferred to the
laboratory. The transportation time was ⬍10 minutes. The vessels
were placed in a glass dish filled with Krebs solution and dissected
free from surrounding fat and connective tissue. All vessels were cut
into 5-mm-long rings and then opened longitudinally and fixed on
the bottom of an organ chamber (volume, 3 mL), with the endothelium side up. The organ chamber was continuously superfused with
Krebs solution bubbled with 95% O2 and 5% CO2 at a constant rate
of 3 mL/min, and the temperature was maintained at 37°C. The
composition of the Krebs solution was as follows (in mmol/L): Na⫹
144, K⫹ 5.9, Ca2⫹ 2.5, Mg2⫹ 1.2, Cl⫺ 128.7, HCO3⫺ 25, SO42⫺ 1.2,
H2PO4⫺ 1.2, and glucose 11. After 60 minutes of incubation, various
procedures were performed.13,14
EDHF and NO in Human IMA and SV
III-297
results in an electrical current. The magnitude of the redox current is
in direct proportion to the concentration of NO in the sample; it is
amplified by the NO meter and registered on a computer (Duo 䡠 18
data recording system, World Precision Instruments). The ISO-NOP
has an inherently high selectivity because the electrodes are separated from the sample in which the measurements are being made by
gas-permeable hydrophobic membranes. This rules out any interference from the solution or any dissolved species other than gas.16
The selectivity of the NO-sensitive electrode was tested in
connection with calibration; in this test, a lack of response to strong
saline solution (3 mol/L) or sodium nitrite (NaNO2, up to
100 ␮mol/L) was taken as evidence of an intact electrode coating.
The electrodes did not respond to ACh (10 ␮mol/L), BK (1 ␮mol/L),
indomethacin (7 ␮mol/L), NG-nitro-L-arginine (L-NNA, 300 ␮mol/
L), or oxyhemoglobin (HbO, 20 ␮mol/L), which were added to the
calibration glass vial.
The membrane-type electrode can be calibrated by chemical
titration using the following equation:
2KNO2⫹2KI⫹2H2SO4⫽2NO⫹I2⫹2H2O⫹2K2SO4
where a known amount of KNO2 is added to produce a known
amount of NO. The quantity (and thus the concentration) of the NO
generated can be calculated directly using stoichiometry if the
concentrations of the reactions are known.18
The calibration was performed daily before the experiment. The
NO-sensitive electrode was inserted into the organ chamber vertically and placed as close to the endothelial surface as possible by
means of a micromanipulator (WR-6, Narishige International). The
NO electrode was connected to the amplifier, and the signals were
recorded. After 60 to 120 minutes of equilibration in the organ
chamber, the electrode was stabilized, and the baseline of the current
became stable. NO measurement was then performed.
The NO concentration measured with the NO-sensitive electrode
reflects the NO released from the endothelium minus the NO cleared
by degradation and diffusion.
Experimental Protocol
Electrophysiological Studies of
EDHF-Mediated Hyperpolarization
A conventional intracellular glass microelectrode filled with 3 mol/L
KCl (tip resistance, 40 to 80 M⍀) was impaled in a smooth muscle
cell from the intimal side. Electrical signals were continuously
monitored on an oscilloscope (BK Precision, Model 2020B and WPI
Electro 705), and the membrane potential was recorded by the
computer (data logging software: PICOLOG, Pico Technology). The
following criteria were used to assess the validity of a successful
impalement: a sudden negative shift in voltage followed by (1) a
stable negative voltage for ⬎2 minutes and (2) an instantaneous
return to the previous voltage level on dislodgement of the microelectrode. Each artery was impaled ⱖ4 times to assess the variability
of the electrophysiological parameters; the results were then averaged to obtain 1 measurement for membrane potential. After a stable
membrane potential for ⱖ2 minutes, acetylcholine (ACh) or bradykinin (BK) was applied.13,14
To investigate EDHF-mediated hyperpolarization in response to
ACh and BK in the IMA and SV, the following substances were
added to the organ chamber to completely inhibit the NO and PGI2
pathway: L-NNA (300 ␮mol/L), an inhibitor of NO synthase;
indomethacin (7 ␮mol/L), a cyclooxygenase inhibitor; and HbO
(20 ␮mol/L), a NO scavenger.19
After 60 minutes of equilibration in the organ chamber, the resting
membrane potentials of the smooth muscle cells of the IMA and SV
were recorded. ACh (⫺8 to ⫺5 log M) or BK (⫺10 to ⫺7 log M)
was added to the organ chamber cumulatively, and the change of the
membrane potential in the smooth muscle cells from the IMA and the
SV was recorded. The organ chamber was then washed with Krebs
solution, and L-NNA (300 ␮mol/L), indomethacin (7 ␮mol/L), and
HbO (20 ␮mol/L) were added to the organ chamber. After incubation and equilibration for another 30 minutes, the aforementioned
steps were repeated, and the change of the membrane potential was
recorded.
Direct Measurement of NO
Direct Measurement of NO
A membrane-type NO-sensitive electrode (ISO-NOP, World Precision Instruments) and isolated NO meter (ISO-NO Mark II, World
Precision Instruments) were used to measure the isolated NO
generated by the vascular endothelium. NO was detected using an
electrochemical method in which a potential is applied to the
measuring electrode relative to the reference electrode, and the
resulting current due to the electrochemical oxidation of NO is
monitored.15–17 The membrane-type NO-sensitive electrode consists
of a working electrode covered by a gas-permeable polymeric
membrane. NO diffuses through the selective membrane or coating
and is oxidized on the surface of the prepolarized electrode, which
To investigate the capacity of NO release from the endothelium of
the IMA and SV, ACh- and BK-induced NO release was examined.
After 60 minutes of incubation and equilibration for each segment in
the organ chamber, ACh (⫺8 to ⫺5 log M) or BK (⫺10 to ⫺7 log
M) was added to the organ chamber cumulatively, and the NO
signals were recorded. The interval between each addition of the
different concentrations of ACh or BK was 15 minutes. The organ
chamber was then washed with Krebs solution, and L-NNA
(300 ␮mol/L), indomethacin (7 ␮mol/L), and HbO (20 ␮mol/L)
were added to the organ chamber. After incubation and equilibration
for another 30 minutes, the aforementioned steps were repeated.
Electrophysiological Study
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Circulation
November 7, 2000
Figure 1. Original tracing of ACh-induced membrane hyperpolarization in smooth muscle cells from IMA (top) and SV (bottom)
in absence of L-NNA, indomethacin, and oxyhemoglobin. ACh
was cumulatively added where indicated by arrows.
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To evaluate the effect of L-NNA on NO release in the IMA and
SV, a subgroup of segments was incubated with L-NNA
(300 ␮mol/L) and indomethacin (7 ␮mol/L) for 30 minutes, and then
the aforementioned steps were repeated. The NO signals were
recorded.
Data Analysis
All results are expressed as means⫾SEM. When comparisons were
made between the IMA and SV groups, an unpaired Student’s t test
(2-tailed) was used. When measurements were performed in the
same vessel segment before and after a treatment, a paired t test was
used. P⬍0.05 was considered significant.
Drugs
Acetylcholine HCl, bradykinin, potassium nitrite (KNO2), potassium
iodide (KI), L-NNA, indomethacin, and oxyhemoglobin were purchased from Sigma. The drugs were prepared in distilled water,
except for indomethacin, which was dissolved in ethanol.
Results
Electrophysiological Study
The resting membrane potential of the smooth muscle cells of
the IMA was higher than that of those from the SV (⫺58⫾1
mV, n⫽15, versus ⫺62⫾1 mV, n⫽23; P⫽0.0001). Mechanical removal of the endothelium produced no significant
changes in the resting membrane potential of either the IMA
(⫺56⫾2 mV, n⫽5; P⫽0.7 versus control) or the SV (⫺61⫾1
mV, n⫽6; P⫽0.5 versus control). Similarly, after incubation
with L-NNA, indomethacin, and HbO for 30 minutes, the
resting membrane potential of the smooth muscle cells from
Figure 3. ACh-induced hyperpolarization in IMA (n⫽10) and SV
(n⫽17) in absence (a) and presence (b) of indomethacin, L-NNA,
and oxyhemoglobin. Vertical error bars are 1 SEM. *P⬍0.05,
**P⬍0.01 compared with SV group (unpaired t test).
the IMA and the SV did not change significantly (IMA:
⫺57⫾2 mV, n⫽8; P⫽0.4 versus control; SV: ⫺60⫾2 mV,
n⫽8; P⫽0.6 versus control).
ACh and BK induced endothelium-dependent hyperpolarization of the smooth muscle cells of the IMA and the SV in
a concentration-dependent manner (Figures 1 through 3).
Without inhibitors, no significant difference existed in the
maximum hyperpolarization induced by ACh or BK in these
2 vessels (Figures 3a and 4a). However, when the NO and
PGI2 pathways were blocked (in the presence of indomethacin, L-NNA, and HbO), ACh- and BK-induced hyperpolarization was reduced in both the IMA and SV. This reduction
(examined in separate experiments in which only 1 concentration of ACh or BK was applied) was more significant in the
SV than in the IMA (ACh ⫺5 log M: 7⫾2 mV, n⫽6, versus
3⫾2 mV, n⫽5; P⬍0.01; BK ⫺7.0 log M: 8⫾1 mV, n⫽6,
versus 4⫾1 mV, n⫽5; P⬍0.05). Therefore, the EDHFmediated hyperpolarization (the residual hyperpolarization)
in the IMA was significantly greater than that in the SV (ACh
⫺5.0 log M: 9.4⫾1.5 mV, n⫽10, versus 4.5⫾1.1 mV, n⫽17;
P⬍0.01; BK ⫺7.0 log M: 10.9⫾1.5 mV, n⫽8, versus
5.1⫾0.5 mV, n⫽8; P⬍0.01) (Figures 3b and 4b). This
hyperpolarization, if expressed as a percentage of the maxi-
Figure 2. Tracings of BK-induced membrane
hyperpolarization of smooth muscle cells from
IMA (left) and SV (right). Indo indicates indomethacin; Hb, oxyhemoglobin; and E-, endothelium-denuded vessels. BK was added
where indicated by arrows.
Liu et al
EDHF and NO in Human IMA and SV
III-299
Figure 5. Original tracing of ACh-induced NO release from endothelium of IMA and SV (from right to left). ACh was added
where indicated by arrows.
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Figure 4. BK-induced hyperpolarization in IMA (n⫽8) and SV
(n⫽8) in absence (a) and presence (b) of indomethacin, L-NNA,
and oxyhemoglobin. Vertical bars are 1 SEM. *P⬍0.05,
**P⬍0.01 compared with SV group (unpaired t test).
mum hyperpolarization without inhibitors, was significantly
greater in the IMA than in the SV (BK ⫺7 log M:
67.9⫾11.4%, n⫽8, versus 43.4⫾21.5%, n⫽8; P⫽0.01).
In the presence of indomethacin, the endotheliumdependent hyperpolarization of the smooth muscle cells did
not change significantly in either the IMA or SV (data not
shown).
In endothelium-denuded IMA and SV segments, the addition of ACh or BK did not cause a significant change in the
membrane potential of the smooth muscle cells.
NO Measurement
Calibrations
The membrane-type NO-sensitive electrodes responded with
increases in current to nanomolar concentrations of NO. The
output current of the probes correlated linearly with the
concentration of NO (r⫽0.9965⫾0.0027, n⫽28 experiments;
P⬍0.005). Because the sensitivity of the different electrodes
varied broadly, from 0.16 to 0.89 nmol 䡠 L⫺1 䡠 pA⫺1 (average,
0.56⫾0.14 nmol 䡠 L⫺1 䡠 pA⫺1), calibration was performed
daily.
Basal Release of NO
In the resting state, a continuous NO signal—the basal release
of NO—was observed in both the IMA and SV. In the IMA,
the basal concentration of NO was 16.8⫾1.6 nmol/L (n⫽13
segments from 8 IMAs), which is significantly greater than
that in the SV (9.9⫾2.8 nmol/L, n⫽13 segments from 9 SVs;
P⬍0.001).
Stimulated Release of NO
Stimulation of the endothelium of the IMA and SV with ACh
and BK evoked a rapid rise in NO that constituted the initial
peak of NO and was followed by a sustained elevation lasting
for 3 to 13 minutes (Figures 5 and 6). The ACh- and
BK-induced NO release in the IMA and SV occurred in a
concentration-dependent manner. Although no significant
differences existed between the IMA and the SV in the peak
concentration of NO release induced by ACh and BK (Figure
7), the duration of NO release in the IMA was significantly
longer than that in the SV (11.6⫾1.5 minutes, n⫽8, versus
8.1⫾1.9 minutes, n⫽9; P⬍0.01; Figure 7).
With regard to the effect of inhibitors on NO release, in the
presence of L-NNA and indomethacin, the ACh- and BKinduced NO release decreased to ⬇26% in the IMA (n⫽5)
and to 29% in the SV (n⫽5), but it was still detectable.
Further addition of HbO (20 ␮mol/L) abolished NO release
(Figure 6).
Discussion
In the present study, we found (1) that the EDHF-mediated
hyperpolarization in the IMA is significantly greater than that
in the SV; (2) that the basal release of NO in the IMA is
significantly greater than that in the SV; and (3) that the
duration of the stimulated release of NO in the IMA is longer
than that in the SV.
To study EDHF-related endothelial function, it is essential
to completely inhibit the other 2 endothelium-derived relaxing factors, NO and PGI2. It was previously demonstrated that
the PGI2 pathway can be blocked by indomethacin,6,7 but
none of the NO synthase inhibitors, such as L-NNA and
N␻-nitro-L-arginine methyl ester, completely blocks NO biosyntheses and release.17,20 NO has been shown to hyperpolarize the vascular smooth muscle cells19,20 and, therefore,
any electrophysiological studies related to EDHF must be
conducted under the condition that the residual NO resistant
to NO synthase inhibitors is completely eliminated. We added
HbO21 in our electrophysiological studies concerning the role
of EDHF, and we demonstrated in the present study that in
the IMA and SV, NO release is completely inhibited by the
combination of L-NNA and HbO. The hyperpolarization of
the smooth muscle cells from the IMA and SV in our study is
therefore related to EDHF.
With the presence of L-NNA and HbO, NO production was
not detectable. Theoretically, a possibility exists that a small
amount of NO could be diffused into the smooth muscle cell
through the endothelium-smooth muscle gap junction. However, it is unlikely that this would affect our results. Martin et
al18 demonstrated that with 10 ␮mol/L HbO, endotheliumdependent relaxation is abolished, which implies that it has
minimal or no influence on the direct diffusion of NO.
Further, HbO also abolishes increases in cGMP. Therefore, in
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Circulation
November 7, 2000
Figure 6. Original tracing of BK-evoked NO release from endothelial cells of IMA and SV (from right to left). Indo indicates indomethacin; Hb, oxyhemoglobin. BK was added at arrows above each recording.
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our study, the possible influence of the diffusion of NO into
the smooth muscle cell is minimal because we used
20 ␮mol/L HbO.
In the present study, for the first time, we demonstrated the
existence of EDHF in the human IMA. In addition, we
showed that the magnitude of EDHF-mediated hyperpolarization elicited by ACh and BK in the IMA is significantly
greater than that in the SV. Interestingly, without NO and
PGI2 inhibitors, endothelium-dependent hyperpolarization is
not different between the IMA and SV. Only after the NO and
PGI2 pathways were completely blocked did the amplitude of
ACh- and BK-induced hyperpolarization, which was mediated by both NO and EDHF, decrease; it decreased by nearly
60% in the SV compared with only 30% in the IMA (Figures
3 and 4). We also observed that when indomethacin was
added, the ACh- and BK-induced endothelium-dependent
hyperpolarization was almost unchanged in both the IMA and
SV. This suggests that the endothelium-dependent hyperpolarization in the IMA and SV is mainly due to EDHF and NO
rather than PGI2. In fact, NO may be responsible for nearly
60% of the endothelium-dependent hyperpolarization induced by ACh and BK in the SV, but only 30% of that in the
IMA (P⫽0.01); therefore, NO makes a greater contribution to
the ACh- and BK-induced hyperpolarization in the SV than
that in the IMA. These data suggest that EDHF might play a
more important role in the IMA than in the SV.
Lüscher et al10 demonstrated that the endotheliumdependent relaxation in the IMA is greater than that in the
SV. Further, using bioassay methods, Pearson et al11 and
Chua et al12 detected the intraluminal release of EDRF from
the IMA and the SV. However, the quantitative measurement
of NO from these vessels has not been reported. With the
Figure 7. Time-course of BK (⫺7.0 log M)-induced NO release
in IMA (n⫽8) and SV (n⫽9). *P⬍0.05 compared with SV group.
recent development of the NO-sensitive electrode, such
measurements became possible. We recently successfully
measured NO release from the coronary artery.17 On the basis
of such experience, in this study, we directly and quantitatively measured NO release in the IMA and SV for the first
time. Although the NO release in the IMA and SV in response
to ACh and BK was in a low nanomolar range, our data are
consistent with the results from another experiment in which
a similar NO meter was used to measure NO release in rat
superior mesenteric artery.15
In the present experiment, we directly measured NO and
demonstrated that the basal release of NO in the IMA was
greater than that in SV. However, the peak concentration of
ACh- and BK-induced NO release in the IMA and SV was
similar, although the duration of NO release in the IMA was
longer. Our findings suggest that the major difference between the IMA and SV is related to the basal release of NO
and stimulated EDHF-mediated hyperpolarization, but not the
stimulated release of NO.
Previous studies showed that endothelium-dependent relaxation in the IMA was greater than that in the SV.10 In
addition, Nishioka et al22 recently reported that, by indirect
measurement, IMA grafts release more endothelium-derived
NO than SV grafts in vivo. These data seem to conflict with
our results. One possible reason for this is that the experimental conditions were different. Moreover, none of these
studies directly and quantitatively measured NO release.
Nishioka et al22 measured NO-related nitrite in coronary
artery bypass grafts in vivo, and their SV grafts were prepared
during harvest. It has been demonstrated that the surgical
preparation of the SV damages the endothelium and abolishes
EDHF-related function.13 In the present study, we used
nondistended SV for the NO measurement. Therefore, it is
understandable that discrepancies exist between our study
and those of others.
It has been demonstrated that NO inhibits platelet and
neutrophil aggregation and adhesion and arrests smooth
muscle cell proliferation.23 These effects are crucial to the
long-term patency of coronary artery bypass grafts. For this
reason, greater basal release of NO in the IMA may contribute significantly to the superior long-term patency of IMA
graft. Further, we recently demonstrated that after surgical
preparation, the NO production from the SV is greatly
Liu et al
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reduced,24 and this may further decrease the patency of the
vein graft.
The contribution of EDHF to endothelium-dependent relaxation varies along the vascular tree.25 In addition, one
study recently showed that under physiological conditions,
continuous release of EDHF contributes to the adjustment of
adequate vascular compliance and tone in the coronary
vascular bed.26 Moreover, some interactions occur between
NO and EDHF. EDHF may play a back-up role when NO
production in the vascular endothelium is impaired,7,17 and
NO may regulate EDHF production and effect.27 A better
understanding of the physiological role of EDHF must await
its biological characterization and the availability of a specific inhibitor for its release and/or action. In fact, a number
of resent studies have focused on the chemical nature of
EDHF.8
Arterial grafts may provide superior long-term patency
than vein grafts.1,2 Our study provides an explanation for this
superior patency: it may be related to the greater basal release
of NO in arterial grafts compared with venous grafts. In
addition, the superior patency may also be related to the more
significant role of EDHF-mediated endothelial function in
arterial grafts. Our study provides a biological basis for the
wide use of arterial grafts in coronary bypass surgery.
Acknowledgments
This study was supported by grants from the Hong Kong Research
Grants Council (HKU7280/97 M and 7246/99 M) and St Vincent
Medical Foundation, Portland, Ore.
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EDHF and NO in Human IMA and SV
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Difference in Endothelium-Derived Hyperpolarizing Factor−Mediated Hyperpolarization
and Nitric Oxide Release Between Human Internal Mammary Artery and Saphenous Vein
Zhi-Gang Liu, Zhi-Dong Ge and Guo-Wei He
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Circulation. 2000;102:Iii-296-Iii-301
doi: 10.1161/01.CIR.102.suppl_3.III-296
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