© 2000 American Heart Association, Inc.
Integrative Physiology |
Production of 20-HETE and Its Role in Autoregulation of Cerebral Blood Flow
From the Cardiovascular Research Center, Department of Physiology (D.G., A.R.L., T.F.L., M.R.T., J.N., H.O., R.J.R., D.R.H.), Department of Pharmacology and Toxicology (K.N., W.B.C.), and Department of Anesthesiology (A.G.H.), Medical College of Wisconsin, Milwaukee, Wis; School of Veterinary Medicine (E.K.B.), University of Pennsylvania, Kennett Square, Pa; and Department of Biochemistry (J.R.F.), University of Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to David R. Harder, PhD, Professor and Director, Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. dharder@post.its.mcw.edu
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Abstract—In the brain, pressure-induced myogenic constriction of cerebral arteriolar muscle contributes to autoregulation of cerebral blood flow (CBF). This study examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated cerebral arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The results of reverse transcriptase–polymerase chain reaction studies revealed that rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8 isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid. Cerebral arterial microsomes incubated with [14C]arachidonic acid produced 20-HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration by 6-fold in cerebral arteries as measured by gas chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE formation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), or its vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure. In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the vasoconstriction action of 20-HETE. Taken together, these data suggest an important role for 20-HETE in the autoregulation of CBF. (Circ Res. 2000;87:60-65.)
Key Words: cerebral blood flow • homeostasis • HETE • cytochrome P-450 • arachidonic acid
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Introduction |
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Blood flow in the brain is normally maintained within narrow limits despite increases in vascular perfusion pressures1 caused by active reductions in arteriolar diameter. This pressure-induced vasoconstriction, known as the myogenic response, has been intensely investigated since its first description by Bayliss nearly a century ago.2 However, the nature of the cellular mechanisms involved have yet to be defined. Vasoconstriction in response to increased intravascular pressure is mediated by changes in the activation state of K+ and/or Ca2+ channels resulting in depolarization of vascular smooth muscle (VSM) and an influx of calcium.3 4 5 6 Activation of phospholipases and protein kinase C (PKC) have also been correlated with the development of myogenic tone,7 8 9 10 11 implicating lipid mediators such as diacylglycerol and arachidonic acid (AA) in this response. Prior studies have also suggested an important role for cytochrome P-450 metabolites of AA in the pressure-induced arterial constriction of cerebral and renal arteries in vitro.12 13 14 15 16 The P-450 metabolite of AA, 20-HETE, is a potent vasoconstrictor, activates PKC and depolarizes VSM by inhibiting the large-conductance KCa channel,12 15 17 18 19 20 21 and increases Ca2+ influx via L-type Ca2+ channels.18 Given that the effects of 20-HETE on ion channels, membrane potential, and PKC mimic those involved in the pressure-induced myogenic response,10 11 we hypothesize that elevations in transmural pressure increase the concentration of 20-HETE in VSM cells, which enhances myogenic constriction of cerebral arterioles. This pressure-induced constriction of cerebral arteries then plays a critical role in autoregulation of cerebral blood flow (CBF) during elevations in arterial pressure.
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Materials and Methods |
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Immunohistochemistry
Cryosectioned (10 to 20 µm) rat brain sample slides were incubated with a polyclonal antibody to P-450 4A enzyme.19 The slides were washed with PBS and incubated with a secondary antibody conjugated to horseradish peroxidase, and P-450 4A immunoreactivity was detected by covering the slides with a 3% solution of H2O2 followed by diaminobenzidine solution for 1 hour.
In Situ Hybridization
A P-450 4A2 cDNA cloned19 from rat kidney was
linearized for in vitro transcription of sense or antisense cRNA. Brain
sections were probed with the labeled cRNA probe, blocked, and
incubated with alkaline phosphatase–conjugated
anti-fluorescein monoclonal antibody (Amersham). Other
sections were stained with Cy3-conjugated anti–smooth muscle 
-actin
monoclonal antibody simultaneously with treatment with the
anti-fluorescein antibody and counterstained with 1% fast
green FCF (Fischer).
Reverse Transcriptase–Polymerase Chain Reaction (RT-PCR)
Poly A+ mRNA was extracted from rat
cerebral microvessels reverse transcribed using poly T primers and
amplified by RT-PCR using forward and reverse primers specific for
cytochrome P-450 4A1, 4A2, 4A3, 4A8, and GAPDH19 having
the following sequences: 4A1 forward, 5'-CTCTTACTTGCCAGAATGGAGAA-3';
4A1 reverse, 5'-GACTTGGATACCCTTGGGTAAAG-3'; 4A2 forward,
5'-AGATCCAAAGCCTTATCAATC-3'; 4A2 reverse,
5'-CAGCCTTGGTGTAGGACCT-3'; 4A3 forward,
5'-CAAAGGCTTCTGGAATTTATC-3'; 4A3 reverse,
5'-CAGCCTTGGTGTAGGACCT-3'; 4A8 forward, 5'-ATCCAGAGGTGTTTGACCCTTAT-3';
4A8 reverse, 5'-AATGAGATGTGAGCAGATGGAGT-3'; GAPDH forward,
5'-CCCCTTCATTGACCTCAACTA; and GAPDH reverse,
5'-ATGCATTGCTGACAATCTTGAG-3'. The specificity of these primer pairs was
tested by amplifying each against 10 ng of the full-length P-450 4A1,
4A2, 4A3, and 4A8 cDNAs we have previously cloned. The PCR products
were separated on a 1% agarose gel and visualized by ethidium bromide
staining.
Cloning and Sequencing of PCR Products
The P-450 4A1, 4A2, 4A3, and 4A8 PCR products were isolated,
ligated into a PCR-2.1 vector (Invitrogen), and used to transfect
INVf competent cells. Plasmid DNA was isolated and sequenced using
the Thermo Sequence dye termination cycle sequencing kit (Amersham) and
a Research Biochemical International (RBI; model 377) sequencer
(Applied Biosystems).
Assays of P-450 Metabolism of AA
Microsomes prepared from bulk isolated cerebral
microvessels20 21 22 were incubated with
[14C]AA in the absence or presence of the
inhibitor of 20-HETE production
N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS)
(50 µmol/L). Reaction products were separated using HPLC as
described previously.18 20 23
Actions of DDMS, 15-HETE, and
20–20-Hydroxyeicosa-6(Z),15(Z)-Dienoic Acid (HEDE) on the KCl-Induced
Contraction of Cerebral Arterial Rings
Rat middle cerebral arterial ring segments were
mounted for tension recording in 2-mL muscle chambers filled
with physiological salt solution (PSS) bubbled with
95% O2 and 5% CO2 at
37°C and pH 7.4. After re-equilibration at 200 mg applied tension, a
control response to 80 mmol/L KCl was determined. After washout,
DDMS (10 µmol/L), 15-HETE (1 µmol/L), and 20-HEDE (1
µmol/L) or vehicle was added to the baths (n=7 to 8 for each group),
and 30 minutes later the response to 80 mmol/L KCl was
redetermined.
Effect of Transmural Pressure on 20-HETE Concentration
Middle cerebral arteries (150 to 200 µm ID) were placed
in a pressure myograph filled with PSS and cannulated as described
previously.4 The endothelium was disrupted
by passing air through the lumen, and its absence was confirmed by a
lack of relaxation to 1 µmol/L acetylcholine. The bathing
solution was composed of (in mmol/L) NaCl 130,
CaCl2 2.5, NaHCO3 15,
MgSO4 1.2,
NaH2PO4 1.2, KCl 4.7,
glucose 5.5, and HEPES 10 and was equilibrated with 95%
O2 and 5% CO2 at 37°C
and pH 7.4. After a 60-minute equilibration period, a pressure-diameter
curve was determined between 20 and 160 mm Hg during control, in
Ca2+-free media, after treatment with DDMS
(10 µmol/L), or after addition of the 20-HETE
antagonist 20-HEDE (1 µmol/L) or 15-HETE (1
µmol/L).24 We also confirmed the actions of the later
compounds on the vasoconstrictor response to 20-HETE in rat isolated
middle cerebral arteries. In a separate study, the arteries were
pressurized at 20 or 140 mm Hg for 30 minutes, removed, and
frozen in liquid N2, and 20-HETE levels were
measured by gas chromatography/mass spectrometry
(GC/MS).
GC/MS Measurement of 20-HETE
Rat cerebral arterial segments were equilibrated at
a transmural pressure of either 20 or 140 mm Hg for 30 minutes,
frozen in liquid N2, and then
homogenized in 10 µL of PBS (pH 7.4). Deuteriated 20-HETE
([2H2]-20-HETE) that
served as an internal standard was added to the homogenate
sample, acidified (pH 3.5), extracted with ethyl acetate, and dried
under stream of N2 gas. The dried sample was
subjected to pentafluorobenzyl-ester derivatization
(-COOH group) and Bis-(trimethylsilyl
trifluoroacetamide)–ether derivatization (-OH group) and
analyzed by GC/MS. The ratio of peak area of m/z=391
to the peak area of m/z=393 (internal standard) was used to
calculate the amount of 20-HETE in the sample.
CBF Autoregulation Studies
Experiments were performed on male Sprague-Dawley rats housed in
the animal care facility of the Medical College of Wisconsin, which is
approved by the Association for Assessment and Accreditation of
Laboratory Animal Care. Rats (250 to 350 g) were
anesthetized with sodium pentobarbital (Nembutal, 50 mg/kg body
weight, IP). The role of 20-HETE in autoregulation of CBF was examined
using laser Doppler flowmetry through a thinned cranial
window25 26 in combination with subdural or
intracerebroventricular (ICV) infusion
of agents that inhibit the formation or the action of 20-HETE. In 10
rats, autoregulation of CBF was measured during the control period and
after ICV infusion of DDMS (50 µmol/L, 1 µL/min), subdural
infusion of 15-HETE (1 µmol/L, 2 µL/min), or ICV infusion of
20-HEDE (1 µmol/L, 2 µL/min).
Statistical Analysis
Data are presented as mean±SEM. The difference in mean
values was determined by 1-way ANOVA with repeated measures, followed
by a Tukey least-significant difference post hoc test. Paired and
unpaired t tests were used where required.
P<0.05 was considered statistically significant.
Drugs and Chemicals
All chemicals were of analytical grade, except where indicated,
and were obtained from Sigma. 15-HETE was purchased from BIOMOL. DDMS
and 20-HETE were synthesized by J.R.F.
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Results |
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Localization of P-450 4A Isoforms in the Cerebral Vasculature
A polyclonal antibody that cross-reacts with rat P-450 4A1, 4A2, and 4A3 isoforms was used to probe sections of rat brain for the presence of immunoreactive protein. Figure 1A
presents the staining pattern
obtained with preimmune serum and demonstrates that there is very
little nonspecific binding. Figure 1B indicates that there is
intense staining for P-450 4A protein in the cerebral
microvasculature.
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To confirm these results, cRNA probes corresponding to P-450 4A2 were
used to localize P-450 4A mRNA in sections of rat brain using in situ
hybridization. Sections of the brain were probed with P-450 sense and
antisense cRNA probes and stained with antibody against vascular smooth
muscle -actin. The antisense cRNA probes hybridized to the wall of
cerebral arteries (Figure 1D
) and colocalized with the pattern
of the -actin staining (Figures 1C and 1D). No detectable
signal was observed in rat brain sections hybridized with sense cRNA
probes.
The high degree of homology between the P-450 4A isoforms suggests that
the antibody and cRNA probes used in the in situ hybridization and
immunohistochemical localization studies likely cross-react with all
members of the P-450 4A family. Therefore, RT-PCR was used to
specifically identify the P-450 4A isoforms expressed in rat cerebral
microvessels. The results presented in Figure 2 demonstrate that mRNAs for P-450 4A1,
4A2, 4A3, and 4A8 isoforms are expressed in cerebral microvessels as
determined by PCR amplification. Subsequent cloning and sequencing of
these PCR products indicated that they were 100% homologous with
the published sequence for these P-450 4A isoforms.19
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Formation of 20-HETE in Rat Cerebral Vessel Microsomes
Incubation of microsomes prepared from rat cerebral arteries with
[14C]AA resulted in the formation of a peak
(Figure 3C) that comigrates with
20-HETE standard.20 Previous GC/MS analysis
confirmed that this peak is 20-HETE.20 Addition of 50
µmol/L DDMS to the incubation blocked the formation of 20-HETE by
cerebral arterial microsomes (Figure 3C). These
results indicate that rat cerebral microvessels synthesize 20-HETE, the
formation of which is inhibited by DDMS.
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Effect of Transmural Pressure on Vascular 20-HETE
Concentration
To determine whether elevation in transmural pressure increases
20-HETE concentration, we measured 20-HETE levels by GC/MS
analysis in pressurized cerebral arteries. Negative ion
chemical ionization GC/MS analysis revealed the presence of a
major ion with a mass-to-charge ratio of 393 for the internal standard
[2H2]20-HETE and 391 for
the biological sample extracted from the pressurized cerebral vessels,
confirming the presence of 20-HETE. As depicted in Figure 4C, an increase in intravascular pressure
from 20 to 140 mm Hg produced a 6-fold increase in 20-HETE
concentration in cerebral arteries (n=5 vessels,
*P<0.01).
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, 10 µmol/L),
the 20-HETE antagonists 20-HEDE (
, 1 µmol/L) and
15-HETE (
, 1 µmol/L), and Ca2+-free PSS (
) on
the pressure-induced constriction of cerebral arteries. Incubation of
middle cerebral arteries with DDMS or addition of 20-HEDE or 15-HETE to
the bath eliminated the pressure-induced constriction of these
arteries, whereas the arterial segments displayed passive
dilation during increases in transmural pressure in
Ca2+-free medium. B, Pressure-active tension relationship
in cerebral arteries. Preincubation with DDMS (10 µmol/L,
Effects of DDMS and Antagonists of 20-HETE on the
Pressure-Induced Constriction of Isolated Cerebral Arteries
The effect of step increases in transmural pressure from 20 to
160 mm Hg on the diameter and active tension of cerebral
arterial segments was determined in the presence and
absence of the cytochrome P-450 inhibitor DDMS or the
20-HETE antagonists, 15-HETE and 20-HEDE.24
Under control conditions, increases in transmural pressure reduced
arteriolar diameter by 48±5% and 53±6% (n=12) at 140 and 160
mm Hg, respectively (Figure 4A). Pretreatment of the vessels
with DDMS (10 µmol/L) for 15 minutes blocked the
pressure-induced constriction and increased diameter to a maximum of
23±5% and 24±6% (n=5) above control at 140 and 160 mm Hg,
respectively (Figure 4A). To rule out the possibility that the
inhibitory actions of DDMS were due to a nonspecific action
of this inhibitor, additional experiments were performed
using structurally and mechanistically different inhibitors
of the vasoconstrictor actions of 20-HETE. In these experiments,
addition of the 20-HETE antagonist 20-HEDE (1
µmol/L, n=4) or 15-HETE (1 µmol/L, n=3) to the bath also
attenuated the pressure-induced constriction of cerebral arteries
(Figure 4A). Application of (in µmol/L) DDMS 10, 20-HEDE
1, or 15-HETE 1 to the bath reduced the increase in active wall tension
by 70%, 49%, and 61% at 160 mm Hg, respectively, and shifted
the pressure-tension curve to the right (Figure 4B). The
contractile response of cerebral arterial rings to 80
mmol/L KCl was not altered after treatment with (in µmol/L) DDMS
10, 20-HEDE 1, or 15-HETE 1. KCl increased tension by 66±23% and
87±21%, 70±15% and 86±16%, and 131±46% and 157±45% before and
after administration of DDMS, 20-HEDE, and 15-HETE, respectively
(P>0.05 for all groups).
Confirmation that 20-HEDE and 15-HETE Block the Vasoconstrictor
Effect of 20-HETE in Cerebral Arteries
The effects of increasing concentrations of 20-HETE
(10–8 to 10–6 mol/L) on
the internal diameter of pressurized (80 mm Hg) cerebral arteries
was determined before and after addition of 20-HEDE (1 µmol/L)
or 15-HETE (1 µmol/L) to the bath. The average basal diameter of
the cerebral arteries pressurized at 80 mm Hg was 64.2±3.0
µm (n=7). Under control conditions, 20-HETE caused
concentration-related reductions in diameter that reached a maximum of
25.3±2% of control in response to 10–6 mol/L
20-HETE. Prior application of 1 µmol/L 20-HEDE or 1
µmol/L 15-HETE to the bath completely blocked the vasoconstrictor
response to 20-HETE (Figure 4D, n=7).
Inhibition of 20-HETE Formation or Its Action Impairs
Autoregulation of CBF
Autoregulation of CBF was studied using a bilateral closed-cranial
window technique25 26 in either pentobarbital- or
chlorolose/urethane-anesthetized rats in vivo. CBF in response
to elevations of systemic arterial blood pressure was
measured using laser Doppler flowmetry. Artificial
cerebrospinal fluid (aCSF) containing 50 µmol/L DDMS was
superfused over 1 cerebral hemisphere, whereas vehicle (aCSF alone) was
superfused over the contralateral hemisphere. Figure 3A depicts
representative tracing of mean arterial
pressure (MAP) and laser Doppler perfusion units (LDPU) for the
right and left hemispheres obtained from a single experiment. Figure 3B summarizes the results from 7 experiments in which
intracranial infusion of DDMS impaired autoregulation of CBF in
pentobarbital-anesthetized rats. The autoregulatory index (AI)
(AI=percentage change in CBF divided by percentage change in MAP) for
these data indicated that blood flow within the control hemisphere was
tightly autoregulated (AI=0.10±0.06; perfect autoregulation is
exhibited at an AI of 0, and no autoregulation is exhibited at an AI of
1.0) over the range of pressures from 70 to 150 mm Hg, whereas
the hemisphere superfused with DDMS displayed a greatly attenuated
autoregulatory response (AI=0.92±0.09). Autoregulation of CBF
recovered after "washout" of DDMS for 30 to 60 minutes. DDMS did
not alter baseline CBF. Similar experiments (n=4) were repeated in rats
anesthetized with cholorose/urethane (225 mg/kg body weight) to
rule out any effect of the anesthetic on the response to DDMS. In these
experiments, DDMS (25 µmol/L) also blocked autoregulation of
CBF. Thus, changing the anesthetic did not influence the results.
The results of the experiments looking at the effects of 20-HETE
antagonists (subdural 15-HETE or DDMS, and ICV 20-HEDE) on
CBF autoregulatory responses are presented in Figure 5. In all animals studied, 15-HETE,
20-HEDE, and DDMS increased the AI. The change in the AI was
significantly greater for 15-HETE, 20-HEDE, or DDMS than that seen in
the time control studies (P<0.05).
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Discussion |
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The results of the present study demonstrate that 20-HETE is produced by rat cerebral microvessels, and immunoreactive protein and mRNA for P-450 4A1, 4A2, 4A3, and 4A8 isoforms are expressed in these vessels. Subsequent GC/MS analysis confirmed the presence of 20-HETE in cerebral arteries and that an elevation in the transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration in these vessels by 6-fold. The rise in 20-HETE concentration with elevation in transmural pressure suggests a role for this endogenous vasoconstrictor in the generation of pressure-induced cerebral vasoconstriction. Our findings that inhibitors of the formation of 20-HETE or blockers of its vasoconstrictor action eliminate the pressure-induced constriction of isolated cerebral arteries indicate that endogenous 20-HETE is an important component of pressure-induced cerebral arterial constriction. The idea that 20-HETE plays an important role in autoregulation of CBF is further supported by the observation that 15-HETE and 20-HEDE, which antagonize the cerebral vasoconstrictor effect of 20-HETE, also attenuated autoregulation of CBF in rats in vivo. Similarly, inhibition of autoregulation of CBF was observed on inhibition of P-450
-hydroxylase with DDMS. Taken
together, these findings suggest that the cytochrome P-450 4A enzymes
and 20-HETE play an important role in the autoregulation of CBF.
20-HETE activates PKC17 27 and modulates the
activities of KCa and L-type
Ca2+ channels,12 17 18 20 28 thereby
depolarizing cerebral VSM cells and promoting
Ca2+ influx, effects that are similar in
character to that of pressure-induced myogenic vasoconstriction.
Activation of PKC leads to sustained VSM contraction, depolarization,
and increased calcium sensitivity of myofilaments.4 29 30 31
The pressure-induced increase in vascular 20-HETE concentration of the
present study suggests that this endogenous metabolite
contributes to the generation of pressure-induced myogenic
vasoconstriction. The recent findings of Dr Michael L. Schwartzman’s
laboratory that overexpression of the cytochrome P-450 4A1 protein and
activity enhances pressure-induced constriction of arteries in vitro
(personal communication, March 2000) also supports our
present findings and further strengthens the role of P-450 4A
-hydroxylase and endogenous 20-HETE in the development
of pressure-induced myogenic vasoconstriction.
DDMS and another P-450 4A -hydroxylase inhibitor,
17-octadecynoic acid, inhibit pressure-dependent vasoconstriction
through blockade of the formation of endogenous 20-HETE
(References 14 15 16 , this study). Consistent
with a previous study using 17-octadecynoic acid,16
inhibition of enzymatic formation of 20-HETE by DDMS did not alter
baseline blood flow in the present study. The lack of effect of
DDMS on baseline CBF is unknown. One possible explanation is that
20-HETE may be stored in tissue or activate a signaling cascade
with sustained effects on vascular tone. Thus, it may take considerable
time to alter baseline tone.
In summary, the present results suggest that cerebral arteries normally produce 20-HETE and that elevation in transmural pressure increases 20-HETE concentration in these vessels. Moreover, inhibitors of the formation of 20-HETE or antagonists of its action attenuate the development of pressure-induced constriction of cerebral arteries in vitro and impair autoregulation of CBF in vivo. These studies further suggest that alterations in the cytochrome P-450 4A activity will alter autoregulation of CBF, which could have a negative impact on neuronal function or result in cerebrovascular pathologies.
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Acknowledgments |
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This work was supported in part by NIH Grants HL-33833, NS-32321, HL-51055, GM-56398, and GM-31278. We thank Kris Hanke for excellent technical assistance.
Received April 3, 2000; accepted May 15, 2000.
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References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Heistad D, Kontos HA. Cerebral circulation. In: Shepherd RS, ed. Handbook of Physiology. Baltimore, Md: Williams & Wilkins; 1983:137–182.
2. Bayliss W. On the local reactions of the arterial wall to changes of internal pressure. J Physiol (Lond). 1902;28:220–231.
3.
D’Angelo G, Meininger GA. Transduction mechanisms
involved in the regulation of myogenic activity.
Hypertension. 1994;23:1096–1105.
4.
Harder DR. Pressure-dependent membrane depolarization
in cat middle cerebral artery. Circ Res. 1984;55:197–202.
5. Harder DR, Kauser K, Roman RJ, Lombard JH. Mechanisms of pressure-induced myogenic activation of cerebral and renal arteries: role of the endothelium. J Hypertension. 1989;7(suppl):S11–S16.
6.
Meininger GA, Zawieja DC, Falcone JC, Hill MA, Davey
JP. Calcium measurement in isolated arterioles during myogenic and
agonist stimulation. Am J Physiol. 1991;261:H950–H959.
7.
Hill MA, Falcone JC, Meininger GA. Evidence for
protein kinase C involvement in arteriolar myogenic reactivity.
Am J Physiol. 1990;259:H1586–H1594.
8.
Karibe A, Watanabe J, Horiguchi S, Takeuchi M, Suzuki
S, Funakoshi M, Katoh H, Keitoku M, Satoh S, Shirato K. Role of
cytosolic Ca2+ and protein kinase C in developing
myogenic contraction in isolated rat small arteries. Am J
Physiol. 1997;272:H1165–H1172.
9.
Narayanan J, Imig M, Roman RJ, Harder DR.
Pressurization of isolated renal arteries increases inositol
trisphosphate and diacylglycerol. Am J Physiol. 1994;266:H1840–H1845.
10.
Osol G, Laher I, Cipolla M. Protein kinase C modulates
basal myogenic tone in resistance arteries from the cerebral
circulation. Circ Res. 1991;68:359–367.
11.
Osol G, Laher I, Kelley M. Myogenic tone is coupled to
phospholipase C and G protein activation in small cerebral arteries.
Am J Physiol. 1993;265:H415–H420.
12. Harder DR, Lange AR, Gebremedhin D, Birks EK, Roman RJ. Cytochrome P450 metabolites of arachidonic acid as intracellular signaling molecules in vascular tissue. J Vasc Res. 1997;34:237–243.[Medline] [Order article via Infotrieve]
13.
Imig JD, Zou AP, Stec DE, Harder DR, Falck JR, Roman
RJ. Formation and actions of
20-hydroxyeicosatetraenoic acid in rat
renal arterioles. Am J Physiol. 1996;270:R217–R227.
14.
Kauser K, Clark JE, Masters BS, Ortiz de Montellano PR,
Ma YH, Harder DR, Roman RJ. Inhibitors of cytochrome
P-450 attenuate the myogenic response of dog renal arcuate
arteries. Circ Res. 1991;68:1154–1163.
15.
Ma YH, Gebremedhin D, Schwartzman ML, Falck JR, Clark
JE, Masters BS, Harder DR, Roman RJ.
20-Hydroxyeicosatetraenoic acid is an
endogenous vasoconstrictor of canine renal arcuate
arteries. Circ Res. 1993;72:126–136.
16.
Zou AP, Imig JD, Kaldunski M, Ortiz de Montellano PR,
Sui Z, Roman RJ. Inhibition of renal vascular 20-HETE
production impairs autoregulation of renal blood flow.
Am J Physiol. 1994;266:F275–F282.
17.
Lange AR, Gebremedhin D, Narayanan J, Harder DR.
20-Hydroxyeicosatetraenoic acid
(20-HETE) induced vasoconstriction and inhibition of
K+ current in cerebral vascular smooth muscle is
dependent on activation of PKC. J Biol Chem. 1997;272:27345–27352.
18.
Gebremedhin D, Lange AR, Narayanan J, Jacobs ER, Harder
DR. Cat cerebral arterial smooth muscle cells produce the
vasoconstrictor 20-HETE which enhances L-type calcium current.
J Physiol (Lond). 1998;507:771–781.
19.
Wang MH, Stec DE, Balazy M, Mastyugin V, Yang CS, Roman
RJ, Schwartzman ML. Cloning, sequencing, and cDNA-directed expression
of the rat renal CYP4A2: arachidonic acid
-hydroxylation and 11,12-epoxidation by CYP4A2 protein. Arch
Biochem Biophys. 1996;336:240–250.[Medline]
[Order article via Infotrieve]
20.
Harder DR, Gebremedhin D, Narayanan J, Jefcoat C, Falck
JR, Campbell WB, Roman RJ. Formation and action of a P-450 4A
metabolite of arachidonic acid in cat cerebral
microvessels. Am J Physiol. 1994;266:H2098–H2107.
21.
Alonso-Galicia M, Drummond H, Reddy KK, Falck JR, Roman
RJ. Inhibition of 20-HETE production contributes to the
vascular responses to nitric oxide. Hypertension. 1997;29:320–325.
22.
Ito O, Alonso-Galicia M, Kathleen AH, Roman RJ.
Localization of cytochrome P4504A isoforms along the rat nephron.
Am J Physiol. 1998;274:F395–F404.
23.
Wang MH, Brand-Schieber E, Zand BA, Nguyen X, Falck JR,
Balu N, Schwartzman ML. Cytochrome P450-derived
arachidonic acid metabolism in the rat
kidney: characterization of selective inhibitors.
J Pharmacol Exp Ther. 1998;284:966–973.
24.
Alonso-Galicia M, Falck JR, Reddy KM, Roman RJ. 20-HETE
agonists and antagonists in the renal circulation.
Am J Physiol. 1999;277:F790–F796.
25.
Alkayed NJ, Birks EK, Hudetz AG, Roman RJ, Henderson L,
Harder DR. Inhibition of brain P-450 arachidonic acid
epoxygenase decreases baseline cerebral blood flow.
Am J Physiol. 1996;271:H1541–H1546.
26. Hudetz A, Roman RJ, Harder DR. Spontaneous flow oscillations in the cerebral cortex during acute changes in mean arterial pressure. J Cereb Blood Flow Metab. 1992;12:491–499.[Medline] [Order article via Infotrieve]
27. Nowicki S, Chen SL, Aizman O, Cheng XJ, Li L, Nowicki C, Nairn A, Greengard P, Aperia A. 20-Hydroxyeicosatetraenoic acid (20-HETE) activates protein kinase C: role in regulation of rat renal Na+,K+-ATPase. J Clin Invest. 1997;99:1224–1230.[Medline] [Order article via Infotrieve]
28.
McCarron JG, Crichton CA, Langton PD, MacKenzie A,
Smith GL. Myogenic contraction by modulation of voltage-dependent
calcium currents in isolated rat cerebral arteries. J
Physiol (Lond). 1997;498:371–379.
29. Carmichael JD, Winder SJ, Walsh MP, Kargacin GH. Calponin and smooth muscle regulation. Can J Physiol Pharmacol. 1994;72:1415–1419.[Medline] [Order article via Infotrieve]
30. Ruzycky AL, Morgan KG. Involvement of the protein kinase C system in calcium-force relationships in ferret aorta. Br J Pharmacol. 1989;97:391–400.[Medline] [Order article via Infotrieve]
31. Walsh MP, Kargacin GJ, Kendrick-Jones J, Lincoln TM. Intracellular mechanisms involved in the regulation of vascular smooth muscle tone. Can J Physiol Pharmacol. 1995;73:565–573.[Medline] [Order article via Infotrieve]
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|
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|
|
|
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