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Department of Pharmacology, New York Medical College, Valhalla, New York 10595
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Studies were conducted on isolated rat gracilis muscle arterioles to examine the role of vascular heme oxygenase (HO)-derived carbon monoxide (CO) on myogenic constrictor responses to stepwise increments in intraluminal pressure. The arterioles express HO-2 but not HO-1 and manufacture CO. Both HO-2 protein expression and CO production are reduced in arterioles maintained for 18 h before experimentation in media containing HO-2 antisense oligodeoxynucleotides (AS-ODN). Pressurization of arterioles mounted on a myograph over the pressure range of 40-100 mmHg elicits reduction of internal diameter. At pressures >40 mmHg, the internal diameter of vessels treated with either HO-2 AS-ODN, the HO inhibitor chromium mesoporphyrin (CrMP), or the K+ channel blocker tetraethylammonium (TEA) are smaller than the corresponding control values. The inclusion of exogenous CO, but not of biliverdin, in the superfusion buffer attenuates pressure-induced vasoconstriction in CrMP-treated vessels. However, exogenous CO does not attenuate pressure-induced vasoconstriction in vessels treated with both CrMP and TEA. Collectively, these data suggest that CO of vascular origin attenuates pressure-induced arteriolar constriction via a mechanism involving a TEA-sensitive K+ channel.
heme oxygenase; potassium channels; vasodilatory mechanisms; vascular reactivity; myogenic tone
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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CARBON MONOXIDE (CO) is a product of heme metabolism by heme oxygenase (HO) isoforms 1 and 2 (16, 25). Exogenous CO relaxes vascular smooth muscle and promotes vasodilation (6, 17, 22). Depending on the vascular preparation, these actions of CO have been linked to activation of soluble guanylate cyclase (4, 19), stimulation of calcium-activated potassium (KCa) channels (25-27), or inhibition of endothelin release from endothelial cells (5, 18).
Arterial vessels express HO-2 constitutively (14, 16, 25), whereas HO-1 is primarily expressed in settings that promote induction of its gene (9, 20). Moreover, arterial vessels manufacture CO (6, 20). CO of vascular origin is thought to subserve a vasodilatory function, based on reports that metalloporphyrins that inhibit HO bring about vasoconstriction (5, 14) or increased vascular reactivity to constrictor agonists (3, 13, 20). However, this conclusion is tentative, because the specificity of HO inhibition with metalloporphyrins has been challenged (8, 23).
According to a recent study, metalloporphyrins with HO inhibitory properties constrict pressurized rat gracilis muscle arterioles, an effect attributed to magnification of myogenic tone (14). The present study was designed to examine the hypothesis that CO of vascular origin modulates myogenic constrictor responses to increments in intraluminal pressure. To this end, we conducted experiments in rat gracilis muscle arterioles with three goals in mind: 1) to quantify the generation of CO and determine whether or not it is HO dependent; 2) to examine the effect of interventions that decrease the activity or expression of HO on the intraluminal pressure-arteriolar diameter relationship; and 3) to investigate involvement of KCa channels in the action of HO-derived CO on myogenic vasoconstriction.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Chemicals. Chromium mesoporphyrin (CrMP) and biliverdin were purchased from Porphyrin Products (Logan, UT), and stock solutions were prepared in 50 mmol/l Na2CO3. CO was purchased from Tech Air (White Plains, NY), and CO-saturated solution (1 mmol/l) was prepared shortly before use (14). Polyclonal HO-1 and HO-2 antibodies were obtained from Stress Gen (Victoria, BC, Canada) and other chemicals from Sigma (St. Louis, MO).
Animals. All animal protocols were approved by the Institutional Animal Care and Use Committee of New York Medical College. Male Sprague-Dawley rats (250-300 g, Charles River; Wilmington, DE) were anesthetized with pentobarbital sodium (60 mg/kg ip), and the gracilis anticus muscles were removed and placed on a dish filled with ice-cold Krebs buffer composed of (in mmol/l) 118.5 NaCl, 4.7 KCl, 2.5 CaCl2, 1.2 KH2PO4, 1.2 MgSO4, 25.0 NaHCO3, and 11.1 dextrose. First-order gracilis muscle arterioles were dissected for use in studies examining 1) the effect of interventions that decrease the expression and/or activity of HO on arteriolar CO generation and on the relationship between intraluminal pressure and the internal diameter of arterioles, and 2) the involvement of vascular smooth muscle KCa channels in the action of CO on myogenic constrictor responsiveness.
Evaluation of the pressure-diameter relationship
Segments (1-2 mm length) of first-order gracilis muscle
arterioles, either pretreated as described below or freshly prepared, were transferred to a water-jacketed vessel chamber (1-ml volume) filled with Krebs buffer containing the nitric oxide synthase inhibitor
N
-nitro-L-arginine methyl ester
(L-NAME, 1 mmol/l) to avoid the confounding influence on
interpretation of results of interactions between the nitric oxide and
CO systems (16, 22). One end of the vessel was mounted on
a glass micropipette connected to a pressure servocontroller (model
CH/200/Q, Living System Instrumentation; Burlington, VT). Subsequently,
the vessel was flushed to remove residual blood and the other end of
the vessel was mounted on a micropipette connected to a stopcock. The
vessel chamber was placed on the stage of a microscope fitted with a
video camera (Javelin; Newburgh, NY) leading to a video caliper (Texas
A & M, College Station, TX), monitor (Javelin), and recorder. Unless indicated otherwise, the vascular preparation was superfused throughout (1 ml/min at 37°C) with L-NAME-containing Krebs buffer
gassed with 95% O2-5% CO2. After the stopcock
was closed, the intraluminal pressure was increased slowly to 80 mmHg,
and the level of pressure was maintained during a 60-min equilibration
period. Only vessels that developed spontaneous tone during
equilibration were utilized.
9 of HO-1 mRNA,
and the sequence of HO-2 AS-ODN is 5'-TCTGAAGACATTGTTGCTGA-3' and
targets bases +11 to 9 of HO-2 mRNA. The sequence of HO-1 S-ODN is
5'-TCCAGCGGCGTCAGCGGTGC-3', and the sequence of HO-2 S-ODN is
5'-GATCTGACTTCAAGTGATTG-3'. Before use, the ODNs were encapsulated in
cationic liposomes (1 µg oligodeoxynucleotide/1 µg liposome)
prepared using
N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (Boehringer- Mannheim; Indianapolis, IN). The
effectiveness of HO-1 AS-ODN and HO-2 AS-ODN in reducing tissue
expression of HO-1 and HO-2, respectively, was documented previously
(1). Freshly dissected gracilis muscle arterioles were
placed on culture dishes (35 mm) containing tissue culture medium only
(Dulbecco's modified Eagle's medium with 10% Nu-serum, 100 µg/ml
streptomycin, and 100 µg/ml penicillin) or tissue culture medium plus
either HO-1 AS-ODN, HO-2 AS-ODN, or the corresponding S-ODN (all at 40 µg/ml). After incubation for 18 h at 37°C in an atmosphere of 95% air-5% CO2, the pressure-diameter relationship was
studied as detailed above. But it is conceivable that the functional
response to an intervention that selectively interferes with HO-2
expression is negated by reciprocal changes in function brought about
by compensatory induction of HO-1 (16). Therefore,
additional experiments were conducted to examine the pressure-diameter
relationship in vascular preparations treated with both HO-1 AS-ODN and
HO-2 AS-ODN combined. The pressure-diameter relationship in vessels
pretreated with both HO-1 AS-ODN and HO-2 AS-ODN also was examined
after the addition of exogenous CO (1-10 µmol/l) to the
superfusion buffer.
In protocol 2, the pressure-diameter relationship was
studied in freshly isolated gracilis muscle arterioles superfused with buffer either containing or not containing CrMP (15 µmol/l), an inhibitor of HO-1 and HO-2 (23). The pressure-diameter
relationship also was examined in vessels superfused with buffer
containing CrMP (15 µmol/l) along with either exogenous CO
(1-100 µmol/l) or biliverdin (10 µmol/l).
In protocol 3, the pressure-diameter relationship was
studied in freshly isolated gracilis muscle arterioles superfused with buffer either containing or not containing tetraethylammonium (TEA, 1.0 mmol/l), a relatively selective blocker of KCa channels (2). The pressure-diameter relationship was also examined
in vessels superfused with buffer containing TEA (1.0 mmol/l), CO (100 µmol/l), and/or CrMP (15 µmol/l).
Patch-clamp studies.
The effect of the HO inhibitor CrMP (15 µmol/l) and CO (10 µmol/l)
on K+ channel currents was studied in smooth muscle cells
isolated from gracilis muscle arterioles (11). Patch-clamp
studies were conducted within 4 h of completing isolation of the
vascular smooth muscle cells (11, 15). K+
currents were recorded using the cell-attached and the inside-out and
outside-out patch configurations. The pipette solution contained (mmol/l) 140 KCl, 1.8 MgCl2, and 10 HEPES (pH 7.4). The
composition of the pipette solution used in outside-out patches was the
same as above except that the concentration of CaCl2 was 10 µmol/l. The composition of the bath solution used in experiments with cell-attached patches was (in mmol/l) 140 NaCl, 5 KCl, 1.8 MgCl2, 1.8 CaCl2, 0.1 8-bromo-cGMP, and 10 HEPES (pH 7.4). The composition of the bath solution used in inside-out
patches was the same as above except that the concentration of
CaCl2 was varied between 0 and 1 µmol/l. 8-Bromo-cGMP was
included in the bath solution to boost the activity of K+
channels, which under resting conditions is low (11). The
open-state probability (NP0) was calculated from
data sampled over a 30- to 60-s interval in the steady state, during
control and experimental periods. The following equation was used
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Analysis of HO proteins and CO release. HO-1 and HO-2 protein expression was assessed in pooled gracilis muscle arterioles (vessels from 10 rats in each pool) incubated for 18 h as detailed above in tissue culture medium containing either HO-2 AS-ODN or HO-2 S-ODN (both at 40 µg/ml). The vessels were homogenized, the homogenate was centrifuged, and the 10,000 g supernatant was analyzed for HO-1 and HO-2 protein by immunoblotting as previously described (14).
Gracilis muscle arterioles maintained for 18 h in culture media containing HO-2 AS-ODN or HO-2 S-ODN were compared by ability to release CO. Vessels so treated were transferred into amber glass vials (2 ml) containing 1.0 ml of Krebs buffer saturated with 95% O2-5% CO2, the vials were capped tightly with rubberized Teflon liners, and the samples were incubated at 37°C for 60 min. The incubations were terminated by placement of the samples on ice. Subsequently, internal standards made of isotopically labeled CO (13C16O and 13C18O) were injected into samples, and the CO content of the headspace gas was determined by gas chromatography/mass spectroscopy. Release of CO was also studied in freshly isolated gracilis muscle arterioles incubated (1 h) as described above in Krebs buffer either containing or not containing CrMP (15 µmol/l). The analyses of CO were performed using a HP-5989A mass spectrometer interfaced to a HP-5890 gas chromatograph. The separation of CO from other gases was carried out on a GS-Molesieve capillary column (30 m, 0.53-mm internal diameter) (J&W Scientific; Folsom, CA) kept at 40°C. Helium was used as the carrier gas with a linear velocity of 0.3 m/s. CO eluted at 3.6 min and was fully separated from N2, O2, H2O, and CO2. The mass spectrometer parameters were 120°C ion source temperature, 31 eV electron energy, and 120°C transfer line temperature. Aliquots (100 µl) of the headspace gas of either standard solutions or experimental samples were injected using a gas-tight syringe into the spitless injector having a temperature of 120°C. Abundance of ions at 28, 29, and 31 mass-to-charge ratio (m/z) corresponding to 12C16O, 13C16O, and 13C18O, respectively, was acquired via selected ion monitoring. The amount of CO in samples was calculated from standard curves constructed with abundance of ions at 28, 29, or 31 m/z. Both standard curves were linear over the range of 0.05-5.0 µmol/l, and both yielded comparable results when used for determining the concentration of endogenous CO. The sensitivity of the assay is 5 pmol of CO. The results were expressed as picomoles of CO in the headspace gas per hour per milligram of protein. The protein content of vascular specimens was measured using the Bio-Rad microassay with bovine serum albumin as the standard.Data analysis. Data are expressed as means ± SE. Data of the pressure-diameter relationship in different groups of vessels were compared by ANOVA followed by the Newman-Keuls post hoc analysis to isolate differences at various levels of pressure. Student's t-test was used to compare data on CO release. The null hypothesis was rejected at P < 0.05.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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CO production and HO expression in gracilis muscle arterioles.
Western blot analysis of proteins in homogenates of pooled gracilis
muscle arterioles maintained in organ culture for 18 h revealed a
protein with the molecular mass of HO-2, but a protein with the
molecular mass of HO-1 was not detected (Fig.
1). The expression of HO-2 protein in
vessels maintained in media containing HO-2 AS-ODN appears to be
reduced compared with that in vessels maintained in media containing
HO-2 S-ODN (Fig. 1). Gracilis muscle arterioles released CO into the
headspace during incubation in Krebs buffer (Fig. 1). CO release from
vessels maintained in media containing HO-2 AS-ODN was less
(P < 0.05) than that from vessels maintained in media
containing HO-2 S-ODN (Fig. 1). CO release from freshly isolated
arterioles incubated for 1 h in buffer containing the HO inhibitor
CrMP (15 µmol/l) (25 ± 9 pmol · mg
1 · h1,
n = 4 experiments) was decreased (P < 0.05) compared with the release from vessels incubated in buffer
without CrMP (162 ± 32 pmol · mg1 · h1,
n = 4 experiments).
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Effect of interventions that decrease CO production on the
pressure-diameter relationship in gracilis muscle arterioles.
Figure 2 displays data on internal
diameter as a function of intraluminal pressure in arterioles
maintained for 18 h before experimentation in culture media with
and without HO-1 AS-ODN, HO-2 AS-ODN, both HO-1 AS-ODN and HO-2 AS-ODN,
or the corresponding S-ODN. Increments of pressure over the range of
0-40 mmHg increased (P < 0.05) the absolute
diameter in all the groups but had little or no effect on the
normalized diameter. Further stepwise increments in pressure to a
maximum of 100 mmHg brought about reductions (P < 0.05) in both the absolute and the normalized diameter. Neither the
absolute diameter nor the normalized diameter of vessels treated with
HO-1 AS-ODN differed from the corresponding values in untreated vessels
or in vessels treated with HO-1 S-ODN over the pressure range of
0-100 mmHg. Similarly, at low intraluminal pressures, both the
absolute diameter and the normalized diameter of vessels treated with
HO-2 AS-ODN or with both HO-1 AS-ODN and HO-2 AS-ODN did not differ
from matching data in untreated vessels or in vessels treated with the
corresponding S-ODN. In contrast, at pressures >40 mmHg, the absolute
diameter and the normalized diameter of vessels treated with HO-2
AS-ODN or with both HO-1 AS-ODN and HO-2 AS-ODN were smaller
(P < 0.05) than the corresponding values in untreated
vessels or in vessels treated, respectively, with HO-2 S-ODN or with
HO-1 S-ODN and HO-2 S-ODN combined. It appears, then, that treatment of
vessels with HO-2 AS-ODN or with both HO-1 AS-ODN and HO-2 AS-ODN
accentuates the constrictor response to increments in intraluminal
pressure over the range of 40-100 mmHg. As shown in Fig.
3, in vessels pretreated with both HO-1 AS-ODN and HO-2 AS-ODN, the inclusion of CO (1-10 µmol/l) in the superfusion buffer attenuated the pressure-induced reduction of both
the absolute and the normalized diameter over the pressure range of
40-100 mmHg.
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Effect of HO inhibition on K+ channel
currents in gracilis arteriole smooth muscle cells.
Figure 6 shows single K+
currents recorded from inside-out patches of smooth muscle cells. In
four experiments in which K+ channel currents were recorded
from a holding potential of 10 mV to 10 mV, the single-channel slope
conductance was 105 ± 5 pS (Fig. 6A). K+
channel currents were absent from patches bathed in
Ca2+-free solution and reappeared when Ca2+ was
reintroduced (Fig. 6B). The inclusion of TEA (1 mmol/l) into the solution facing the cytoplasmic side of the patch decreased K+ channel activity; it also reduced the channel current
amplitude, which is a characteristic of the TEA-induced fast blockade
(Fig. 6C). K+ channel activity recorded in
outside-out patches was decreased by the inclusion of iberiotoxin (100 nmol/l) into the solution in contact with the extracellular side of the
excised patch (Fig. 6D).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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CO is produced in tissues via HO-dependent and HO-independent pathways (24). We found that gracilis muscle arterioles incubated in Krebs buffer release CO. The CO released from these vessels is primarily manufactured via a HO-dependent pathway, because treatment of the vessels with the HO inhibitor CrMP decreased CO release to about 16% of control. Gracilis muscle arterioles express HO-2 but not HO-1 in the basal state (14). Our study shows that HO-2 protein expression is decreased in arterioles maintained under culture conditions for 18 h in media containing HO-2 AS-ODN. Moreover, the release of CO from vessels treated with HO-2 AS-ODN is reduced compared with that from vessels treated with HO-2 S-ODN. Collectively, these observations indicate that HO-2 contributes to the manufacture of CO in gracilis muscle arterioles in the basal state. Under special circumstances, HO-1 also contributes to generation of CO in vascular tissue. For example, CO production is increased in the aorta of rats subjected to conditions that bring about induction of vascular HO-1 (20).
Previous studies (21) documented that stepwise increments in intraluminal pressure over the range of 40-120 mmHg bring about constriction of isolated rat gracilis muscle arterioles via a mechanism intrinsic to the smooth muscle of arterioles. We found that pressure-induced constrictor responses are magnified in vessels treated with either CrMP, HO-2 AS-ODN, or both HO-1 AS-ODN and HO-2 AS-ODN. Treatment with CrMP also decreased the threshold for expression of pressure-induced arteriolar constriction. In contrast, pressure-induced constrictor responses were not enhanced by treatment with either HO-1 AS-ODN, HO-1 S-ODN, or HO-2 S-ODN. These results suggest that reduction of HO-2 expression or activity brings about intensification of vasoconstrictor responses to increments in pressure. Such intensification of pressure-induced arteriolar constriction may be the manifestation of diminished vascular production of a HO-2 product that exerts a tonic inhibitory influence of myogenic vasoconstriction.
In our study, pressure-induced constrictor responses in gracilis muscle arterioles superfused with buffer containing CrMP alone were equally magnified as in vessels superfused with buffer containing both CrMP and the HO product biliverdin (10 µmol/l). In contrast, pressure-induced constrictor responses in vessels treated with CrMP were attenuated by the inclusion of CO (10 and 100 µmol/l) into the superfusion buffer. Inclusion of CO (1 and 10 µmol/l) into the superfusion buffer also decreased the intensity or pressure-induced constrictor responses in vessels treated with both HO-1 AS-ODN and HO-2 AS-ODN. These observations suggest that CO, rather than biliverdin, is the product of heme metabolism by vascular HO-2, which inhibits myogenic vasoconstriction. A preliminary study suggested that CO of vascular origin also attenuates the sensitivity of rat renal interlobar arteries to phenylephrine (13). Therefore, vascular CO may be the key protagonist of a regulatory mechanism that reduces the reactivity of vascular smooth muscle to both myogenic and hormonal stimuli. In accord with this notion, other investigators have reported that the reactivity to constrictor agonists is decreased in rat aortas and tail arteries subjected to conditions that induce HO-1 expression (3, 20, 25, 26).
In the present study, treatment of gracilis arteriole smooth muscle cells with CrMP reduced the NPo of a 105-pS K+ channel requiring Ca2+ for activation and inhibited by TEA and iberiotoxin. That CrMP did not reduce the activity of this channel in inside-out membrane patches of smooth muscle cells argues against direct inhibition of the channel by the HO inhibitor. Rather, the inhibitory effect of CrMP on K+ channel activity of cell-attached patches may be due to diminished synthesis of HO-derived CO. This is supported by the observation that exogenous CO increased the open probability of the 105-pS K+ channel in smooth muscle cells pretreated with CrMP, reversing the effect of the HO inhibitor. Previously, other investigators demonstrated that exogenous CO stimulates a 238-pS KCa channel in smooth muscle cells of rat tail artery by increasing the calcium sensitivity of this high-conductance channel (27). Collectively, these observations suggest that CO produced in vascular smooth muscle cells stimulates K channels activated by Ca2+ and inhibited by TEA and iberiotoxin.
Previous studies (2, 10) have suggested participation of KCa channels in the regulation of membrane potential and tone in small myogenically active arteries studied in vitro. For example, blockade of KCa channels with TEA was reported to bring about depolarization and constriction of pressurized cerebral arteries (2). The constrictor response to TEA was attributed to enhancement of myogenic tone, reflecting interference with the function of a negative feedback pathway involving KCa channels, which controls the degree of membrane depolarization and, consequently, the level of myogenic tone (2). Our present in vitro study of gracilis muscle arterioles provides evidence consistent with such an inhibitory influence of KCa channels on myogenic vasoconstriction. We found that the inclusion of TEA into the superfusion buffer greatly increased the sensitivity and the intensity of the constrictor response to increments in pressure, mimicking the effect of CrMP on the pressure-diameter relationship. Because treatment of gracilis arteriole smooth muscle cells with CrMP decreases the activity of a 105-pS K+ channel sensitive to TEA, the possibility arises that the intensification of pressure-induced constrictor responses in vessels treated with CrMP is linked to reduction in the NPo of KCa channels in vascular smooth muscle due to a decrease in CO production. In this regard, we found that pressure-induced constrictor responses were equally increased by treatment of the vessels with TEA alone or with both TEA and CrMP concurrently, which is consistent with a common mechanism accounting for the effects of TEA and the HO inhibitor on the pressure-diameter relationship. We also found that the inclusion of exogenous CO (100 µmol/l) into the superfusion buffer did not attenuate pressure-induced constriction in vessels treated with both TEA and CrMP. Altogether, these results suggest that CO of vascular origin attenuates pressure-induced vasoconstriction via a mechanism that involves KCa channels. These findings relate to the developing concept that endogenous CO plays a role in the regulation of vascular tone and blood pressure (12).
In summary, this study provides information on the generation of CO by rat gracilis muscle arterioles, the influence of endogenous CO on pressure-induced vasoconstriction, and the involvement of K+ channels in the modulatory action of CO on myogenic vasoconstriction. We found that gracilis muscle arterioles manufacture CO via a HO-2-dependent pathway, which in turn, reduces pressure-induced vasoconstriction by activating KCa channels in vascular smooth muscle. On the basis of these findings, it is tempting to speculate that CO manufactured by resistance vessels participates in the regulation of vascular tone and tissue perfusion by serving as an endogenous activator of KCa channels in vascular smooth muscle, thus exerting an inhibitory influence on the reactivity of vascular smooth muscle to constrictor stimuli. But the extrapolation of conclusions derived from our studies in vitro to more physiological settings in vivo can be challenged on several grounds. KCa channels were reported not to play a role in the regulation of myogenic tone in cremaster muscle arterioles in vivo (11) and, therefore, may not be targets for an inhibitory action of endogenous CO on myogenic vasoconstriction in vivo. The regulatory effectiveness of arteriolar CO in vivo may be reduced by the presence of red blood cell hemoglobin that scavenges CO. In physiological settings where endothelial cell nitric oxide synthesis undergoes tonic stimulation by shear stress, arteriolar CO may exert an inhibitory action on endothelial nitric oxide synthase that brings about vasoconstriction rather than vasodilation (22). These are among the issues that need to be addressed in the future to gain a fuller appreciation of the role of CO of vascular origin in the regulation of vasomotor tone in vivo.
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ACKNOWLEDGEMENTS |
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We thank Jennifer Brown for assistance.
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FOOTNOTES |
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This work was supported by National Institutes of Health Grants HL-18579, HL-34300, and DK-56601 and by American Heart Association, New York Affiliate, Grants 00-20152T and 99-30291T.
Address for reprint requests and other correspondence: F. Zhang, Dept. of Pharmacology, New York Medical College, Valhalla, New York 10595 (E-mail: Fan_Zhang{at}nymc.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.
Received 25 September 2000; accepted in final form 9 March 2001.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Abraham, NG,
and
daSilva JL.
Different physiological functions of heme oxygenase isoforms in endothelial cells (EC) (Abstract).
FASEB J
12:
A323,
1998.
2.
Brayden, JE,
and
Nelson MT.
Regulation of arterial tone by activation of calcium-dependent potassium channels.
Science
256:
532-535,
1992
3.
Caudill, TK,
Resta TC,
Kanagy NL,
and
Walker BR.
Role of endothelial carbon monoxide in attenuated vasoreactivity following chronic hypoxia.
Am J Physiol Regulatory Integrative Comp Physiol
275:
R1025-R1030,
1998
4.
Christodoulides, N,
Durante W,
Kroll MH,
and
Schafer AI.
Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide.
Circulation
91:
2306-2309,
1995
5.
Coceani, F.
Control of the ductus arteriosus: a new function for cytochrome P450, endothelin and nitric oxide.
Biochem Pharmacol
48:
1315-1318,
1994[ISI][Medline].
6.
Cook, NM,
Marks K,
Nakatsu GS,
McLaughlin BE,
Vreman HJ,
and
Stevenson DK.
Heme oxygenase activity in the adult rat aorta and liver as measured by carbon monoxide formation.
Can J Physiol Pharmacol
73:
515-518,
1995[ISI][Medline].
7.
Furchgott, RF,
and
Jothianandan D.
Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light.
Blood Vessels
28:
52-61,
1991[ISI][Medline].
8.
Grundemar, L,
and
Ny L.
Pitfalls using metallopophyrins in carbon monoxide research.
Trends Pharmacol Sci
18:
193-195,
1997[Medline].
9.
Ishizaka, N,
De Leon H,
Laursen JB,
Fukui T,
Wilcox JN,
DeKeulenaer G,
Griendling KK,
and
Alexander RW.
Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta.
Circulation
96:
1923-1929,
1997
10.
Jackson, WF.
Ion channels and vascular tone.
Hypertension
35:
173-178,
2000
11.
Jackson, WF,
and
Blair KL.
Characterization and function of Ca2+-activated K+ channels in arteriolar muscle cells.
Am J Physiol Heart Circ Physiol
274:
H27-H34,
1998
12.
Johnson, RA,
Lavesa M,
Askari B,
Abraham NG,
and
Nasjletti A.
A heme oxygenase product, presumably carbon monoxide mediates a vasodepressor function in rats.
Hypertension
25:
166-169,
1995
13.
Kaide, JI,
Zhang F,
Yu C,
Abraham NG,
and
Nasjletti A.
Heme oxygenase (HO)-2 derived carbon monoxide (CO) is an inhibitory regulator of small renal artery (SRA) reactivity to phenylephrone (Abstract).
Hypertension
34:
366,
1999.
14.
Kozma, F,
Johnson RA,
Zhang F,
Yu C,
Tong X,
and
Nasjletti A.
Contribution of endogenous carbon monoxide to regulation of diameter in resistance vessels.
Am J Physiol Regulatory Integrative Comp Physiol
276:
R1087-R1094,
1999
15.
Liu, H,
Mount DB,
Nasjletti A,
and
Wang W.
Carbon monoxide (CO) stimulates the 70 pS K+ channel of the rat thick ascending limb.
J Clin Invest
103:
963-970,
1999[ISI][Medline].
16.
Maines, MD.
The heme oxygenase system: a regulator of second messenger gases.
Annu Rev Pharmacol Toxicol
37:
517-554,
1997[ISI][Medline].
17.
McLaughlin, BE,
Chretien ML,
Choi C,
Brien JF,
Nakatsu K,
and
Marks GS.
Potentiation of carbon monoxide-induced relaxation of rat aorta by YC-1[3-(5'-hydroxymethyl-1'-furyl)-benzylindazole].
Can J Physiol Pharmacol
78:
343-349,
2000[ISI][Medline].
18.
Morita, T,
and
Kourembanas S.
Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide.
J Clin Invest
96:
2676-2682,
1995.
19.
Morita, T,
Perrella MA,
Lee ME,
and
Kourembanas S.
Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP.
Proc Natl Acad Sci USA
92:
1475-1479,
1995
20.
Sammut, IA,
Foresti R,
Clarck JE,
Exon DJ,
Vesely MJJ,
Sarathchandra P,
Green CJ,
and
Motterlini R.
Carbon monoxide is a major contributor to the regulation of vascular tone in aortas expressing high levels of haeme oxygenase-1.
Br J Pharmacol
125:
1437-1444,
1998[ISI][Medline].
21.
Sun, D,
Kaley G,
and
Koller A.
Characteristics and origin of myogenic response in isolated gracilis muscle arterioles.
Am J Physiol Heart Circ Physiol
266:
H1177-H1183,
1994
22.
Thorup, C,
Jones CL,
Gross SS,
Moore LC,
and
Goligorsky MS.
Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS.
Am J Physiol Renal Physiol
277:
F882-F889,
1999
23.
Vreman, HJ,
Ekstrand BC,
and
Stevenson DK.
Selection of metalloporphyrin heme oxygenase inhibitors based on potency and photoreactivity.
Pediatr Res
33:
195-200,
1993[ISI][Medline].
24.
Vreman, HJ,
Wong RJ,
Sanesi CA,
Dennery PA,
and
Stevenson DK.
Simultaneous production of carbon monoxide and thiobarbituric acid reactive substances in rat tissue preparations by an iron-ascorbate system.
Can J Physiol Pharmacol
76:
1057-1065,
1998[ISI][Medline].
25.
Wang, R.
Resurgence of carbon monoxide: an endogenous gaseous vasorelaxing factor.
Can J Pharmacol
76:
1-15,
1998.
26.
Wang, R,
Wang Z,
and
Wu L.
Carbon monoxide-induced vasorelaxation and the underlying mechanisms.
Br J Pharmacol
121:
927-934,
1997[ISI][Medline].
27.
Wang, R,
Wu L,
and
Wang Z.
The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells.
Pflügers Arch
434:
285-291,
1997[ISI][Medline].
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