Stroke. 1997;28:1264-1271
(Stroke. 1997;28:1264-1271.)
© 1997 American Heart Association, Inc.
Role of Potassium Channels in Relaxations of Canine Middle Cerebral Arteries Induced by Nitric Oxide Donors
Hisashi Onoue, MD, PhD;
Zvonimir S. Katusic, MD, PhD
From the Departments of Anesthesiology and Pharmacology, Mayo Clinic and
Mayo Foundation, Rochester, Minn.
Correspondence to Zvonimir S. Katusic, MD, PhD, Departments of Anesthesiology and Pharmacology, Mayo Clinic, Rochester, MN 55905.
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Abstract
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Background and Purpose The mechanisms underlying smooth
muscle
relaxations of cerebral arteries in response to nitric oxide
(NO)
and cyclic GMP (cGMP) are still not completely understood. The
present
study was designed to determine the role of potassium
channels
in the relaxations to NO donors 3-morpholinosydnonimine
(SIN-1)
and sodium nitroprusside (SNP), as well as 8-bromo-3',5'-cGMP
(a
synthetic analogue of cGMP) and zaprinast (a selective cGMP
phosphodiesterase
inhibitor).
Methods Rings of canine middle cerebral arteries without
endothelium were suspended in Krebs-Ringer bicarbonate
solution for isometric tension recording. The levels of cGMP
were measured by radioimmunoassay. Relaxations to NO donors
8-bromo-cGMP and zaprinast were studied in the presence and in the
absence of K+ channel blockers charybdotoxin
(large-conductance Ca2+-activated K+
channels), glyburide (ATP-sensitive K+ channels),
4-aminopyridine (delayed rectifier K+
channels), and BaCl2 (multiple types of K+
channels).
Results Concentration-dependent relaxations caused by NO
donors (SIN-1 and SNP) were significantly reduced in arteries treated
with BaCl2 (3x10-4 mol/L) or
charybdotoxin (3x10-8 mol/L). Relaxations to
8-bromo-cGMP were not affected by the same concentrations of
BaCl2 and charybdotoxin; however, they were reduced by
higher concentrations of BaCl2
(3x10-3 mol/L) and charybdotoxin
(10-7 mol/L). Zaprinast-induced relaxations
were significantly reduced by BaCl2
(3x10-4 mol/L) or charybdotoxin
(3x10-8 mol/L). Glyburide
(10-5 mol/L) and
4-aminopyridine (10-3 mol/L)
did not alter the relaxations to SIN-1 or SNP. The production
of cGMP stimulated by SIN-1 in the vascular smooth muscle was not
affected by BaCl2 (3x10-3 mol/L)
or charybdotoxin (10-7 mol/L).
Conclusions These results indicate that in canine middle
cerebral arteries, a significant portion of relaxations to NO liberated
from nitrovasodilators is mediated by large-conductance
Ca2+-activated K+ channels. Other
K+ channels, sensitive to BaCl2, may also be
involved in the mechanism of relaxations induced by NO.
Key Words: cerebral arteries cyclic GMP nitric oxide vasodilation dogs
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Introduction
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Nitric oxide is a major
mediator of endothelium-dependent relaxations
in
various vascular beds.
1 2 It is generally accepted that
NO
and exogenous nitrovasodilators relax smooth muscle cells
by activation
of the soluble form of guanylate cyclase and subsequent
production
of cGMP.
3 However, the precise
mechanisms underlying vascular
smooth muscle relaxations via NO and
cGMP still remain to be
defined. In recent years,
electrophysiological and pharmacological
studies
demonstrated an important role of K
+ channels in
the hyperpolarization
and relaxations of smooth
muscle cells.
4 5 6 Several studies
have suggested that
native endothelium-derived relaxing factor/NO
and NO
liberated from nitrovasodilators can activate K
+
channels
in blood vessels. Although NO reportedly activates
large-conductance
K
Ca through cGMP-dependent protein
kinase,
7 8 9 it has been
also demonstrated that NO itself
can directly (independently
of cGMP) activate K
Ca
in rabbit aortic smooth muscle cells.
10
NO plays an essential role in regulation of the cerebral
circulation,11 12 and impaired NO-mediated relaxations
appear to be involved in the pathogenesis of cerebral vasospasm
associated with subarachnoid
hemorrhage.13 14 15 Recent evidence suggests that
several types of K+ channels, including KCa,
KATP, KIR, and KDR, are functional
in cerebral blood vessels.16 17 18 19 20 The role of K+
channels in mediation of vasodilation to NO has not been studied in
large cerebral arteries. Therefore, the present study was designed
to determine whether activation of K+ channels may play a
role in NO-induced relaxations of isolated canine middle cerebral
arteries.
 |
Materials and Methods
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The experiments were performed on rings (4 mm long) of
middle
cerebral arteries taken from dogs (15 to 20 kg)
anesthetized
with 30 mg/kg IV pentobarbital sodium. All
procedures were conducted
in accordance with institutional guidelines.
The arterial rings
were placed in modified Krebs-Ringer
bicarbonate solution (control
solution) of the following millimolar
composition: NaCl 118.3,
KCl 4.7, CaCl
2 2.5,
MgSO
4 1.2, KH
2PO
4 1.2,
NaHCO
3 25.0, calcium
EDTA 0.026, and glucose 11.1. In all
rings, the endothelium
was removed mechanically by
gentle rubbing of the intimal surface
with a stainless-steel wire
(31-gauge diameter).
21 Each ring
was connected to an
isometric force-displacement transducer
(Grass FT03, Grass Instrument
Co) and suspended in an organ
chamber filled with 25 mL control
solution (37°C, pH 7.4)
aerated with 94% O
2-6%
CO
2. Isometric tension was recorded continuously.
The
rings were allowed to stabilize at a resting tension of
0.2 to 0.4
g for 1 hour. Each ring was then gradually stretched
to the optimal
point of its length-tension curve (approximately
3.0 g) as
determined by the contraction to 10
-5 mol/L
UTP.
22 The successful removal of
endothelium was verified by the absence
of relaxation
induced by 10
-6 mol/L
bradykinin.
23
Radioimmunoassay of cGMP
A radioimmunoassay technique was used to determine the levels of
cGMP. Rings without endothelium were initially
incubated in control solution bubbled with a 94% O2-6%
CO2 gas mixture and maintained at 37°C. After 1 hour, the
rings were incubated for an additional 30 minutes in a solution
containing 10-3 mol/L IBMX to inhibit the
degradation of cGMP by phosphodiesterases. During the last 10 minutes
of the incubation period, some arteries were treated with SIN-1
(10-6 mol/L). To determine the effect of
K+ channel blockers on production of cGMP,
BaCl2 (3x10-3 mol/L) or
charybdotoxin (10-7 mol/L) was added to the
solution 10 minutes before the addition of SIN-1. To determine the
effect of zaprinast on cGMP levels, control rings were not treated with
IBMX, whereas treated rings were incubated in a solution containing
10-3 mol/L zaprinast for 30 minutes. After the
incubation, the rings were immediately removed from the solution and
frozen in liquid nitrogen. cGMP radioimmunoassay kits (Amersham) were
used to perform the measurements. Protein assay was performed by DC
Protein Assay Kit (Bio-Rad).
Drugs
The following pharmacological agents were used: UTP (Sigma
Chemical Co), bradykinin (Sigma), SIN-1 (Molecular Probes), SNP
(Sigma), 8-bromo-cGMP (Sigma), zaprinast (BIOMOL Research
Laboratories, Inc), diltiazem hydrochloride (Sigma), BaCl2
(Sigma), charybdotoxin (Sigma), glyburide (BIOMOL),
4-aminopyridine (Research Biochemicals International),
and papaverine hydrochloride (Sigma). Drugs were dissolved in distilled
water; volumes of <0.15 mL were added to the organ chambers. Stock
solutions of zaprinast and glyburide were prepared in DMSO (Sigma).
Concentrations of all drugs are expressed as final molar (moles per
liter) concentration in the control solution. The rings were contracted
with 10-5 mol/L UTP 10 minutes before the
addition of vasodilator agents. Concentration-response curves were
obtained in a cumulative fashion. Several rings prepared from the same
artery were studied in parallel, and a concentration-response curve was
established by each preparation. The relaxations were expressed as a
percentage of maximal relaxations induced by
3x10-4 mol/L papaverine. The drugs used as
K+ channel blockers were added 20 minutes before obtaining
the concentration-response curve for each vasodilator agent.
K+ channel blockers (except glyburide) caused contractions
of quiescent middle cerebral arteries (Table 1
).
However, because UTP produced only small contractions in the rings
already contracted by K+ channel blockers, absolute values
of tension did not differ significantly between the control arteries
and arteries treated with K+ channel blockers (see figure
and table legends). In certain experiments, the EC50 was
calculated for each ring by linear interpolation between the two
concentrations evoking responses just above and below 50% of the
maximal response.
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Table 1. Effect of BaCl2,
Charybdotoxin, and 4-Aminopyridine on Resting Tension
of Canine Middle Cerebral Artery Rings Without
Endothelium
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Statistical Analysis
The results are expressed as mean±SEM; n refers to the number
of animals studied. Statistical evaluation of the data was performed by
ANOVA, followed by Fisher's test. Statistical significance was
accepted at the level of P<.05.
 |
Results
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Effects of K+ Channel Blockers on Relaxations to NO
Donors SIN-1 and SNP
BaCl
2 (3x10
-5 to
3x10
-3 mol/L) caused concentration-dependent
reduction
of relaxations to SIN-1 (Fig 1

). The effect
was significant
in the presence of 3x10
-4 and
3x10
-3 mol/L BaCl
2; these
concentrations
of BaCl
2 also significantly reduced maximal
relaxations to SIN-1.
In the presence of increasing concentrations of
charybdotoxin
(10
-8 to
10
-7 mol/L), relaxations to SIN-1 were also
significantly
reduced (Fig 2

). Small but significant
reduction of maximal
relaxations to SIN-1 was detected in the presence
of the highest
concentration (10
-7 mol/L) of
charybdotoxin. The inhibitory
effect of
3x10
-3 mol/L BaCl
2 on relaxations
to SIN-1 was significantly
greater than that of
10
-7 mol/L charybdotoxin (Fig 3A

); however,
the effect of
3x10
-4 mol/L BaCl
2 was identical
to inhibition
observed in the presence of 10
-7
mol/L charybdotoxin (Fig 3A

).
Further significant reduction of
relaxations to SIN-1 was obtained
in arteries treated with
charybdotoxin (10
-7 mol/L) plus
BaCl
2 (3x10
-4 mol/L) compared
with arteries treated with charybdotoxin
alone (Fig 3B

).

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Figure 1. Concentration-response curves to SIN-1 in canine
middle cerebral artery rings without endothelium in the
absence (control) and presence of BaCl2
(3x10-5, 3x10-4,
and 3x10-3 mol/L). Relaxations were obtained
during contractions induced by 10-5 mol/L UTP.
Data are shown as mean±SEM and are expressed as percent of maximal
relaxations induced by 3x10-4 mol/L
papaverine; 100%=3.85±0.41 g (n=12), 4.88±0.51 g (n=5), 4.21±0.45 g
(n=9), and 5.34±0.73 g (n=5) for control rings and rings treated with
3x10-5, 3x10-4, and
3x10-3 mol/L BaCl2, respectively.
*Significantly different from control; P<.05.
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Figure 2. Concentration-response curves to SIN-1 in canine
middle cerebral artery rings without endothelium in the
absence (control) and presence of charybdotoxin (CTX;
10-8, 3x10-8, and
10-7 mol/L). Relaxations were obtained during
contractions induced by 10-5 mol/L UTP. Data
are shown as mean±SEM and are expressed as percent of maximal
relaxations induced by 3x10-4 mol/L
papaverine; 100%=4.43±0.39 g (n=10), 4.00±0.39 g (n=5), 5.44±0.92 g
(n=5), and 5.00±0.81 g (n=5) for control rings and rings treated with
10-8, 3x10-8, and
10-7 mol/L CTX, respectively. *Significantly
different from control; P<.05.
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Figure 3. Concentration-response curves to SIN-1 in canine
middle cerebral artery rings without endothelium in the
absence (control) and presence of BaCl2
(3x10-4 and 3x10-3
mol/L) and charybdotoxin (CTX; 10-7 mol/L) (A)
and in the absence (control) and presence of CTX
(10-7 mol/L) alone and CTX
(10-7 mol/L) plus BaCl2
(3x10-4 mol/L) (B). Relaxations were obtained
during contractions induced by 10-5 mol/L UTP.
Data are shown as mean±SEM and are expressed as percent of maximal
relaxations induced by 3x10-4 mol/L
papaverine; 100%=4.01±0.58 g (n=9), 4.21±0.45 g (n=9), 5.34±0.73 g
(n=5), and 5.00±0.81 g (n=5) for control rings and rings treated with
3x10-4 and 3x10-3
mol/L BaCl2, and 10-7 mol/L CTX
(A) and 4.18±0.47 g (n=6), 4.93±0.68 g (n=6), and 4.65±1.00 g (n=6)
for control rings and rings treated with CTX and CTX+BaCl2
(B), respectively. *Significantly different from rings treated with
3x10-4 mol/L BaCl2 or
10-7 mol/L CTX (A) and from rings treated with
10-7 mol/L CTX alone (B);
P<.05.
|
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The relaxations to SNP were also inhibited by BaCl2 and
charybdotoxin in the same manner as those to SIN-1 (Figs 4
and 5
).

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Figure 4. Concentration-response curves to SNP in canine
middle cerebral artery rings without endothelium in the
absence (control) and presence of BaCl2
(3x10-5, 3x10-4,
and 3x10-3 mol/L). Relaxations were obtained
during contractions induced by 10-5 mol/L UTP.
Data are shown as mean±SEM and are expressed as percent of maximal
relaxations induced by 3x10-4 mol/L
papaverine; 100%=3.98±0.32 g (n=12), 4.26±0.90 g (n=5), 4.26±0.59 g
(n=9), and 5.26±0.68 g (n=5) for control rings and rings treated with
3x10-5, 3x10-4, and
3x10-3 mol/L BaCl2, respectively.
*Significantly different from control; P<.05.
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Figure 5. Concentration-response curves to SNP in canine
middle cerebral artery rings without endothelium in the
absence (control) and presence of charybdotoxin (CTX;
10-8, 3x10-8, and
10-7 mol/L). Relaxations were obtained during
contractions induced by 10-5 mol/L UTP. Data
are shown as mean±SEM and are expressed as percent of maximal
relaxations induced by 3x10-4 mol/L
papaverine; 100%=4.20±0.28 g (n=10), 4.80±0.24 g (n=5), 4.72±0.57 g
(n=5), and 5.28±0.73 g (n=5) for control rings and rings treated with
10-8, 3x10-8, and
10-7 mol/L CTX, respectively. *Significantly
different from control; P<.05.
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Glyburide (10-5 mol/L) and
4-aminopyridine (10-3 mol/L)
did not alter values of EC50 and maximal relaxations
induced by SIN-1 or SNP (Tables 2
and 3
).
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Table 2. Effect of Glyburide on EC50and Maximal Relaxations Obtained in Response to SIN-1 and SNP in
Canine Middle Cerebral Arteries Without Endothelium
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Table 3. Effect of 4-Aminopyridine on
EC50 and Maximal Relaxations Obtained in Response to
SIN-1 and SNP in Canine Middle Cerebral Arteries Without
Endothelium
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Effects of K+ Channel Blockers on Relaxations to
8-Bromo-cGMP
In contrast to NO donors, the relaxations to 8-bromo-cGMP were not
affected by 3x10-4 mol/L BaCl2
and 3x10-8 mol/L charybdotoxin (Fig 6A
and 6B
). However, BaCl2
(3x10-3 mol/L) and charybdotoxin
(10-7 mol/L) significantly suppressed the
responses to 8-bromo-cGMP.

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Figure 6. Concentration-response curves to 8-bromo-cGMP in
canine middle cerebral artery rings without endothelium
in the absence (control) and presence of BaCl2
(3x10-4 and 3x10-3
mol/L) (A) and in the absence (control) and presence of charybdotoxin
(CTX; 3x10-8 and
10-7 mol/L) (B). Relaxations were obtained
during contractions induced by 10-5 mol/L UTP.
Data are shown as mean±SEM and are expressed as percent of maximal
relaxations induced by 3x10-4 mol/L
papaverine; 100%=3.93±0.33 g (n=9), 4.26±0.65 g (n=5), and
5.21±0.73 g (n=7) for control rings and rings treated with
3x10-4 and 3x10-3
mol/L BaCl2 (A) and 3.65±0.34 g (n=13), 3.68±0.41 g
(n=5), and 4.08±0.50 g (n=8) for control rings and rings treated with
3x10-8 and 10-7
mol/L CTX (B), respectively. *Significantly different from control;
P<.05.
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Effects of K+ Channel Blockers on Relaxations to
Zaprinast
The relaxations induced by zaprinast
(10-7 to 10-4 mol/L)
were significantly reduced by BaCl2
(3x10-4 mol/L) or charybdotoxin
(3x10-8 mol/L; Fig 7
).

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Figure 7. Concentration-response curves to zaprinast in canine
middle cerebral artery rings without endothelium in the
absence (control) and presence of BaCl2
(3x10-4 mol/L) and charybdotoxin (CTX;
3x10-8 mol/L). Relaxations were obtained
during contractions induced by 10-5 mol/L UTP.
Data are shown as mean±SEM and are expressed as percent of maximal
relaxations induced by 3x10-4 mol/L
papaverine; 100%=4.44±0.26 g (n=6), 4.50±0.39 g (n=6), and
4.86±0.48 g (n=6) for control rings and rings treated with
BaCl2 and CTX, respectively. *Significantly different from
control; P<.05.
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Effects of K+ Channel Blockers on Relaxations to
Diltiazem
Diltiazem-induced relaxations were not affected by
BaCl2 and charybdotoxin even in the presence of the highest
concentrations of 3x10-3 and
10-7 mol/L, respectively. EC50
(-log mol/L) and maximal relaxations to diltiazem detected in the
absence or presence of BaCl2
(3x10-3 mol/L) were 6.30±0.08 and
87.8±2.0% (n=10) and 6.32±0.09 and 95.3±1.3% (n=5), respectively.
Those in the presence of charybdotoxin (10-7
mol/L) were 6.45±0.08 and 91.1±2.2% (n=5).
Effects of K+ Channel Blockers on Production
of cGMP
In canine middle cerebral arteries without
endothelium, SIN-1 (10-6
mol/L) produced approximately a 10-fold increase in levels of cGMP. The
increase in cGMP levels was not affected by the highest concentrations
of BaCl2 (3x10-3 mol/L) and
charybdotoxin (10-7 mol/L; Fig 8
).

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Figure 8. Effect of SIN-1 (10-6
mol/L) on cGMP levels in canine middle cerebral arteries without
endothelium and modification by BaCl2
(3x10-3 mol/L) and charybdotoxin (CTX;
10-7 mol/L) of the increased cGMP
production. Values are expressed as mean±SEM (n=10).
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Effects of Zaprinast on cGMP Levels
In canine middle cerebral arteries without
endothelium, zaprinast (10-3
mol/L) caused a significant increase in cGMP levels (Fig 9
).

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Figure 9. Effect of zaprinast (10-3
mol/L) on cGMP levels in canine middle cerebral arteries without
endothelium. Values are expressed as mean±SEM (n=7).
*Significantly different from control; P<.05.
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Discussion
|
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The results of the present study demonstrate that
K
Ca play an
important role in mediation of cerebral
arterial relaxations
to NO. This conclusion is based on the
experiments demonstrating
that a selective large-conductance
K
Ca inhibitor,
charybdotoxin,
5 24 25 26 reduced the relaxations induced by
two chemically
different NO donors, SIN-1 and SNP.
3
Selectivity of charybdotoxin
was confirmed by the fact that relaxations
to a calcium channel
antagonist, diltiazem, were not
affected in the presence of
the highest concentration of charybdotoxin
(10
-7 mol/L). Furthermore,
charybdotoxin did
not affect production of cGMP stimulated by
SIN-1, ruling out
the possibility that the inhibitory effect
of charybdotoxin
is due to nonselective inactivation of guanylate
cyclase.
Our findings are in agreement with conclusions of the
previous in vivo
study performed in rat cerebral arterioles.
27 However, we
extended previous observations to demonstrate that
K
Ca
mediate a significant portion of relaxations to NO in large
canine
cerebral arteries.
BaCl2 also strongly reduced the relaxations to NO donors
without having any effect on relaxations to diltiazem or
production of cGMP. These results further supported the
proposition that K+ channels play an important role in
cerebral arterial relaxations to NO. However, previous
studies demonstrated that even at the very high concentration of
10-2 mol/L, BaCl2 has little
effect on KCa.5 28 The highest concentration
of BaCl2 used in our study was
3x10-3 mol/L, suggesting that the effect of
BaCl2 is possibly mediated via K+ channels
other than KCa. This conclusion is also supported by the
fact that the inhibitory effect of BaCl2 on
relaxations to NO donors was significantly larger than the
inhibitory effect of charybdotoxin. Furthermore, in
arteries treated with a high concentration of charybdotoxin
(10-7 mol/L), a lower concentration of
BaCl2 (3x10-4 mol/L) exerted an
additional inhibitory effect on relaxations to SIN-1,
suggesting that charybdotoxin and BaCl2 may affect
different populations of K+ channels. KIR are
most sensitive to extracellular barium ions and should be blocked by
micromolar concentrations of BaCl25 29 30 31 32 ;
however, the relaxations to SIN-1 and SNP were not reduced in the
presence of 3x10-5 mol/L BaCl2.
These observations minimize the possibility that KIR
activation is involved in the relaxant actions of nitrovasodilators. In
addition, our results demonstrated that glyburide
(10-5 mol/L), a selective KATP
inhibitor,5 17 33 34 and
4-aminopyridine (10-3 mol/L),
the most reliable KDR
inhibitor,5 18 35 36 did not affect the
relaxations to SIN-1 or SNP, ruling out a contribution of these
K+ channels to NO-induced relaxations. The results of our
study do not allow any conclusion regarding the type of K+
channels responsible for a BaCl2-sensitive component of
relaxations to nitrovasodilators. Interestingly, in canine colonic
smooth muscle cells, NO activates K+ channels that
are resistant to known specific K+ channel
blockers.37 This finding is in agreement with our results,
and it is very likely that in canine middle cerebral artery, NO may
activate a population of K+ channels that cannot be
characterized by the available pharmacological tools used in the
present study.
In contrast to NO donors, the relaxations to a cGMP analogue,
8-bromo-cGMP, were not affected by 3x10-4
mol/L BaCl2 and 3x10-8 mol/L
charybdotoxin. Such selective inhibition of relaxations to NO donors by
K+ channel blockers suggests that NO may directly
(independently of cGMP) activate K+ channels.
Although previous studies using patch-clamp techniques have documented
that NO activates large-conductance KCa through
cGMP-dependent protein kinase in calf thoracic aorta,7
rabbit basilar artery,8 and rat pulmonary
artery,9 it has also been reported that NO itself can
directly activate KCa in rabbit aortic smooth
muscle cells.10 Therefore, it is possible that a similar
direct effect of NO is involved in the mechanisms of relaxation in
canine cerebral arteries. Another possibility is that SIN-1 and SNP may
generate peroxynitrite and cyanide, respectively,38 39 and
that these products may activate K+ channels
independently of cGMP production. However, we obtained
identical results with two different NO donors, suggesting that our
findings are best explained by formation of NO rather than
peroxynitrite or cyanide. More importantly, the relaxations to
zaprinast, which selectively inhibits cGMP phosphodiesterase and
thereby increases endogenous cGMP levels,40 41 42
were strongly reduced by 3x10-4 mol/L
BaCl2 or 3x10-8 mol/L
charybdotoxin. Furthermore, the relaxations to 8-bromo-cGMP were
reduced by higher concentrations of BaCl2
(3x10-3 mol/L) or charybdotoxin
(10-7 mol/L), suggesting that the relaxations
caused by exogenous cGMP are also mediated partly by the activation of
K+ channels. An exact reason for the lower sensitivity of
8-bromo-cGMPinduced relaxations to K+ channel blockers is
not clear. One possible explanation is that exogenous cGMP may not have
access to the same molecular targets as endogenous cGMP
generated after guanylate cyclase activation or
phosphodiesterase inhibition. Thus, our results suggest that the
activation of K+ channels by NO donors is most likely
mediated by increased production of cGMP. It remains to be
determined whether cGMP-independent interaction between NO and
K+ channels is an important mechanism of relaxations in
cerebral arteries.
The results of the present study suggest that in canine cerebral
arteries, large-conductance KCa on the smooth muscle play a
role in mediation of relaxations to NO. The activation of
KCa appears to be dependent on cGMP production.
Other K+ channels, sensitive to BaCl2, may also
be involved in the mechanism of relaxations induced by NO. These
findings provide a basis for further analysis of the
physiological and pathological significance of NO
in the regulation of the cerebral circulation.
 |
Selected Abbreviations and Acronyms
|
|---|
| 8-bromo-cGMP |
= |
8-bromo-3',5'-cyclic GMP |
| cGMP |
= |
cyclic GMP |
| IBMX |
= |
3-isobutyl-1-methylxanthine |
| KATP |
= |
ATP-sensitive K+ channels |
| KCa |
= |
Ca2+-activated K+ channels |
| KDR |
= |
delayed rectifier K+ channels |
| KIR |
= |
inward rectifier K+ channels |
| NO |
= |
nitric oxide |
| SIN-1 |
= |
3-morpholinosydnonimine |
| SNP |
= |
sodium nitroprusside |
|
 |
Acknowledgments
|
|---|
This work was supported in part by National Heart, Lung, and
Blood
Institute grant HL-53524 and by the Mayo Foundation. Dr Onoue
was
supported by a scholarship from Uehara Memorial Foundation
(Tokyo,
Japan).
Received November 21, 1996;
revision received March 5, 1997;
accepted March 28, 1997.
 |
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