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(Hypertension. 1999;34:659-665.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Activation of AT2 Receptors by Endogenous Angiotensin II Is Involved in Flow-Induced Dilation in Rat Resistance Arteries
From the Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 141 (K.M., L.L., B.I.L., D.H.) and Unit 127 (C.H.), IFR 6, Université Paris VII, France.
Correspondence to D. Henrion, PhD, INSERM Unit 141, Hopital Lariboisiere, 41 Blvd de la Chapelle, 75475 Paris, cedex 10, France. E-mail daniel.henrion{at}inserm.lrb.ap-hop-paris.fr
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Abstract |
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Abstract—Pressure-induced tone (myogenic, MT) and flow (shear stress)–induced dilation (FD) are potent modulators of resistance artery tone. We tested the hypothesis that locally produced angiotensin II interacts with MT and FD. Rat mesenteric resistance arteries were perfused in situ. Arterial diameter was measured by intravital microscopy after a bifurcation on 2 distal arterial branches equivalent in size (150 µm, n=7 per group). One was ligated distally and thus submitted to pressure only (MT, no FD). The second branch was submitted to flow and pressure (MT and FD). The difference in diameter between the 2 vessels was considered to be FD. Flow-diameter-pressure relationship was established in the absence and then in the presence of 1 of the following agents. In the nonligated segment (MT+FD), angiotensin II type 1 (AT1) receptor blockade (losartan) had no significant effect, whereas angiotensin II type 2 (AT2) receptor blockade (PD123319) or saralasin (AT1+AT2 blocker) decreased the diameter significantly, by 9±1 and 10±0.8 µm, respectively. Angiotensin II in the presence of losartan increased the diameter by 18±0.6 µm (inhibited by PD123319). PD123319 or saralasin had no effect after NO synthesis blockade or after endothelial disruption. In the arterial segment ligated distally (MT only), AT1 or AT2 receptor blockade had no significant effect. AT2-dependent dilation represented 20% to 39% of FD (shear stress from 22 to 37 dyn/cm2), and AT2-receptor mRNA was found in mesenteric resistance arteries. Thus, resistance arterial tone was modulated in situ by locally produced angiotensin II, which might participate in flow-induced dilation through endothelial AT2 receptor activation of NO release.
Key Words: blood vessels • myogenic • arteries • stress, mechanical • angiotensin II • bradykinin
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Introduction |
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Flow (shear stress)–induced vasodilation and pressure (tensile stress)–induced tone (myogenic tone) play a key role in the control of vascular tone.1 2 3 4 5 6 In resistance arteries, pressure or stretch induces myogenic tone,6 7 8 which is opposed by flow-induced dilation, in vitro as well as in vivo.3 5 6 8 9 Whereas myogenic tone is mainly independent of endothelial factors,6 8 shear stress has been widely shown to induce the release of endothelium-derived vasoactive agents.1 4 5 10 11
The local tissue renin-angiotensin system12 13 14 is another potent regulator of vascular tone. At physiological concentrations, angiotensin II amplifies agonist-induced contractions.13 14 15 Angiotensin II also activates nitric oxide (NO) production by vascular endothelial cells through angiotensin II type 1 receptor (AT1) activation16 or through angiotensin II type 2 (AT2) receptor activation.17 18 Although no relation between flow-induced dilation and angiotensin II is known as yet, angiotensin II production may be activated by stretch in cardiac myocytes.19 20 Moreover, in the aorta, stretch and angiotensin II synergistically activate DNA and protein synthesis.21 Nevertheless, the role of angiotensin II in the functional response of resistance arteries to pressure and to flow is not yet known. We hypothesized that locally produced angiotensin II might play a role in the acute response (changes in diameter) of resistance arteries to pressure (myogenic tone) and/or to flow (flow-induced dilation).
In rat mesenteric resistance arteries perfused in situ, arterial diameter was measured after a bifurcation on 2 distal branches equivalent in size. One branch was perfused, and the other was ligated distally, so that it was submitted to an identical pressure but not to flow. Thus, in 1 branch (ligated), myogenic tone developed only on pressure stimulation, and in the other branch (left open), myogenic tone was opposed by flow-induced dilation. The difference in diameter between the 2 branches can be considered to be due to flow-induced dilation.
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Methods |
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Mesenteric Artery In Situ
Twelve-week-old normotensive rats were anesthetized (sodium pentobarbital, 50 mg/kg IP), a medial laparotomy was performed, and the last loop of the small intestine was exposed and placed into a container allowing the superfusion of the preparation. The following physiological salt solution (PSS) was used (mmol/L): NaCl 130, NaHCO3 14.9, KCl 3.7, CaCl2 · 2H2O 1.6, KH2PO4 1.2, MgSO4 · 7H2O 1.2, glucose 11, and HEPES 10, and albumin 4%. Temperature was 37°C to 38°C, pH 7.4, PO2 160 mm Hg, and PCO2 37 mm Hg. Two segments of a mesenteric resistance artery, equivalent in size, were dissected free of fat and connective tissues (Figure 1). One branch was perfused (154±6.4 µm OD, n=28), and the other was ligated distally, so that it was submitted to pressure but not to flow (158±6.8 µm OD before ligation, n=28). A video camera (Pulnix, CCIR) mounted on a binocular lens allowed recording and analysis of the image of the isolated arterial segments. A polyethylene catheter (OD 0.6 mm, ID 0.28 mm) was placed in the first-generation branch of the mesenteric artery and connected to a syringe infusion pump (Harvard Apparatus) driving a 10-mL syringe (Becton Dickinson). One second-order branch was left open, and a 10-cm-long catheter, connected to a pressure transducer (Gould P10EZ), was inserted into an arterial branch located upstream of the observed segment of artery to record the mesenteric arterial pressure. Flow was measured in the perfused arterial segment with a Transonic T106 small-animal blood flowmeter (Transonic systems Inc). Step increases in flow were performed, and each flow rate was maintained for 3 minutes. The arterial video images, arterial pressure, and flow were recorded continuously. Data were collected (Biopac data acquisition system, MP 100), recorded, and analyzed (Acqknowledge software, Biopac). Shear stress was calculated for each individual segment of artery as previously described11 :
=4
· Q/
· r3, where is
viscosity (poise=dyn · s-1 ·
cm-2), Q is flow (mL/s), and r is radius
(cm).
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Experimental Protocol
Flow-pressure-diameter relationships were established by
imposing step increases in flow from 75 to 298 µL/min to the
mesenteric arteries. Step increases in flow and diameter measurement
were conducted under control conditions and after the addition to the
superfusion PSS of 1 the following drugs for 30 minutes:
losartan (10 µmol/L, n=7) or candesartan cilexetil (10
nmol/L) was used as a specific AT1 receptor
blocker, PD 123319 (0.1, 1, or 10 µmol/L, n=5 to 7) as a
specific AT2 receptor blocker, perindopril
(10 µmol/L, n=7) or captopril (10 µmol/L, n=3) as
angiotensin-converting enzyme inhibitors
(ACEIs),
[Sar1-Ala8]angiotensin
II (saralasin, 10 µmol/L, n=7) as a nonspecific
AT1 and AT2 receptor
blocker, and HOE 140 (0.1 µmol/L) as a specific bradykinin
B2 receptor blocker. Only 1 drug was used per
experiment. Drugs were added to the superfusate so that both
the ligated and the nonligated vessels were submitted to the same
concentration of drug. Drugs added extraluminally to the bath of
isolated vessels diffuse rapidly through the vascular
wall.13
The effect of PD 123319 (1 µmol/L, 30 minutes) on the arterial diameter was also investigated in vessels in which the endothelium had been removed by a perfusion of 1 mL of CO2 at a flow rate of 150 µL/min11 14 16 (n=7) or in vessels pretreated with the NO synthesis blocker NG-nitro-L-arginine methyl ester (L-NAME, 10 µmol/L, 30 minutes, n=7).
In a separate series of experiments (n=7), angiotensin II (0.1 nmol/L) was perfused in mesenteric arteries pretreated with candesartan cilexetil (10 nmol/L).
At the end of each experiment, flow steps and diameter measurements were conducted in the presence of sodium nitroprusside (1 mmol/L) or EGTA (2 mmol/L) and in the absence of extracellular Ca2+ to determine artery passive diameter.10 11 13
Mesenteric Resistance Artery: In Vitro Preparation
Mesenteric artery segments 
100 µm in ID were isolated
and cannulated at both ends and mounted in a video-monitored perfusion
system as previously described.13 22 23 Briefly, the
artery segment was bathed in a 5-mL organ bath containing PSS (changed
at a rate of 4 mL/min). Intraluminal pressure (100 mm Hg) was
controlled by a servo perfusion system, and the arterial
diameter was measured and recorded continuously with a video
monitoring system (Living System Instrumentation Inc). Arteries were
submitted to flow (0 to 150 µL/min), and this was subsequently
repeated after addition of PD 123319 (1 µmol/L, n=7). Passive
diameter was then determined.13 22 23 24 Results are given
in micrometers for artery diameters and flow-induced
relaxation.22 23 24 In another series of experiments (n=6),
angiotensin II (0.1 nmol/L) was perfused in mesenteric
arteries after pretreatment of the vessels with the
AT1 receptor blocker candesartan cilexetil (10
nmol/L).
Reverse Transcription–Polymerase Chain Reaction Analysis
of AT2 Receptors
AT2 receptor mRNA expression was
measured by reverse transcription–polymerase chain reaction (RT-PCR).
Total RNA was extracted from mesenteric arteries (n=6) with Trizol
(Gibco Life Technologies). RT was performed in a reaction volume of 20
µL containing 100 ng RNA, 0.4 µmol/L reverse primer, 2.5
mmol/L dNTP, 6 µL of BRL 5x buffer, 0.6 µL oligo(dT) 12 to 18
primer (0.5 µg/µL), 200 U Moloney murine leukemia virus reverse
transcriptase, RNAse inhibitor 50 U, and dithiothreitol
10 mmol/L at 39°C for 90 minutes. The reaction was
inactivated at 70°C for 10 minutes. The resulting cDNA
was amplified with specific primers. For amplification of
AT2 receptor cDNA, the sense primer was
5'-TGAGTCCGCATTTAACTGC-3' (extending from base 86 to 105), and the
antisense primer was 5'-ACCACTGAGCATATTTCTCGGG-3' (extending from base
600 to 622). For GAPDH, the sense primer was
5'-TGAAGGTCGGTGTCAACGGATTTGGC-3', and the antisense primer was
5'-CATGTAGGCCATGAGGTCCACCAC-3'. The amplification profile involved
denaturation at 94°C, annealing at 53°C, and extension at 72°C
for 30 cycles. The PCR products were separated on a 5%
polyacrylamide gel, and radioactivity was measured.
Western Blot Analysis of AT2 Receptors
Mesenteric arteries (n=4) were homogenized with
Vibra-Cell (Bioblock Scientific). The homogenate was
incubated on ice for 30 minutes in ice-cold lysis buffer B (20
mmol/L Tris-HCl [pH 7.5], 5 mmol/L EGTA, 150 mmol/L NaCl,
20 mmol/L glycerophosphate, 10 mmol/L NaF, 1 mmol/L
sodium orthovanadate, 1% Triton X-100, 0.1% Tween-20, 1 µg/mL
aprotinin, 1 mmol/L PMSF, 0.5 mmol/L TPCK, and 0.5
mmol/L TLCK) at a ratio of 0.3 mL/10 mg wet wt. Extracts were incubated
on ice for 15 minutes and then centrifuged
(15 000g, 15 minutes, 4°C). The protein concentration was
determined with Micro BCA Protein Assay Kit (Pierce). After
denaturation at 100°C for 5 minutes, equal amounts of proteins (20
µg) were loaded on a 9% polyacrylamide gel and transferred
to nitrocellulose membranes for 12 hours at 65 V at 4°C. Membranes
were blocked with 5% nonfat dry milk in TBST (20 mmol/L Tris [pH
8.0], 150 mmol/L NaCl, and 0.1% Tween-20) for 1 hour and were
then incubated with rabbit polyclonal antibody against
AT2 receptors (50 kDa) (Eurogentec) diluted 1:100
or 1:200 in washing solution at room temperature for 1 hour. The
membranes were then washed, incubated with anti-rabbit horseradish
peroxidase–conjugated second antibody 1:2000 for 1 hour at room
temperature, and washed extensively. An enhanced chemiluminescence
system was used as the detection method. Blots were washed and
subjected to autoradiography. Molecular weights of
proteins were estimated by use of prestained markers (Bio-Rad,
161-0324). Each lane presented in a single panel of the gel
picture was from the same gel and the same exposure of the
autoradiogram.
Immunofluorescence Analysis of
AT2 Receptors
Segments of a mesenteric resistance artery were mounted in
embedding medium (Miles, Inc), frozen in isopentane previously cooled
in liquid nitrogen, and stored at -80°C.
Immunostaining analysis was performed as
previously described23 on transverse cross sections 5
µm thick incubated overnight at 4°C with
anti-AT2 antibodies (Eurogentec) at a dilution of
1:200 and then incubated for 30 minutes at 37°C with anti-rabbit
antibodies conjugated to FITC (Amersham). Fluorescence staining
was visualized with a epifluorescence microscope (Leica).
Control experiments were performed to verify the specificity of the
antibodies in which the second antibody only was present or in
which the first antibody (anti-COX-2–specific antibody) only was
present. In these series of controls, no autofluorescence
was observed.
Drugs
Losartan was provided by Dupont-Merck Pharmaceutical, PD
123319 by Parke-Davis, perindopril by Servier, HOE 140 by Hoechst AG,
and cadesartan cilexetil by Astra Hässle. Other reagents were
purchased from Sigma Chemical Co.
Statistical Analysis
Results are expressed as mean±SEM. Significance of the
differences between groups was determined by 2-way ANOVA for
consecutive measurements (flow rates) or by 1-way ANOVA followed by a
Dunnett's test when appropriate. Values of P<0.05 were
considered to be significant.
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Results |
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Phenylephrine-induced tone and acetylcholine-induced dilation were performed before the experimental protocol to test smooth muscle contractility and the presence of the endothelium. Phenylephrine (1 µmol/L) induced a significant decrease in arterial diameter from 158±5 to 86±3 µm (n=35). After this preconstriction with phenylephrine, acetylcholine (10 µmol/L) induced a significant increase in arterial diameter, from 86±3 to 155±8 µm (n=35).
Flow-diameter and pressure-diameter relationships determined in mesenteric resistance arteries under control conditions, in situ, are shown in Figure 2. OD and intraluminal pressure increased when flow was raised by steps. Diameter values were significantly lower in the distally ligated arterial segments (submitted to pressure but not to flow) than in the segments left open and submitted to both pressure and flow. Flow-induced dilation could be estimated as the difference between the diameter in the vessel submitted to both pressure and flow and the diameter of the vessel submitted only to pressure (Figure 2, bottom). Flow rates measured in the arterial segment left open (with flow) ranged from 75±4.5 to 298±4.6 µL/min (n=35). These flow rates corresponded to mesenteric arterial pressures ranging from 48±4 to 71±4 mm Hg. Passive diameter (maximal dilation), determined for each flow step (as given above) in the presence of EGTA (2 mmol/L) or sodium nitroprusside (0.1 mmol/L) and in the absence of extracellular calcium, ranged from 172±3 to 197±4 µm.
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The ACEI perindopril (10 µmol/L, n=7) induced a significant increase in diameter in the mesenteric arterial branch submitted to pressure without flow and in the branch submitted to flow and pressure (Figure 3, top). Captopril (10 µmol/L, n=3) had an effect similar to that of perindopril (Figure 3, middle).
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Bradykinin B2 receptor blockade (HOE 140, 0.1 µmol/L, n=7), after pretreatment with the ACEI perindopril (10 µmol/L), induced a significant decrease in diameter in the mesenteric arterial branches submitted to flow and pressure and in the mesenteric arterial branches submitted to pressure only (Figure 3, bottom). When bradykinin B2 receptor blockade (HOE 140, 0.1 µmol/L) was used without pretreatment with perindopril, no significant change in diameter occurred in the mesenteric artery branches submitted to flow and/or pressure (0.5±1.0- to 1.8±1.6-µm change in diameter, vessels with flow, n=5, P=NS and 1.2±0.9- to 2.2±1.8-µm change in diameter, vessels with flow, n=5, P=NS).
AT1 receptor antagonism with losartan (10 µmol/L) or with candesartan cilexetil (10 nmol/L) induced no significant change in diameter in the mesenteric arterial branches submitted either to flow and pressure or to pressure only (Figure 4).
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AT2 receptor antagonism with PD 123329 (0.1, 1, or 10 µmol/L) induced a concentration-dependent decrease in diameter in mesenteric arterial branches submitted to flow and pressure (Figure 5). The effect of PD 123319 (10 µmol/L) was not affected by a pretreatment of the vessels with losartan (10 µmol/L) (1±1.1- to 0.5±1.2-µm change in diameter, n=5). In the mesenteric arterial branches submitted to pressure only, PD 123319 (1 or 10 µmol/L) induced no significant changes in diameter (Figure 5). Nonselective AT1 and AT2 receptor blockade with saralasin (10 µmol/L) significantly decreased the arterial diameter in the mesenteric branches submitted to flow and pressure, not in the arterial branches submitted to pressure only (Figure 5). Similarly, saralasin (10 µmol/L) significantly decreased the arterial diameter (9.2±1.6- to 7.5±1.4-µm decrease in diameter for flow rates ranging from 75 to 298 µL/min) in the mesenteric branches submitted to flow and pressure in presence of losartan (10 µmol/L).
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The AT2 receptor antagonist PD 123329 (10 µmol/L) had no significant effect when used in a vessel pretreated with L-NAME (Figure 6, top) or after endothelium removal (Figure 6, bottom). Inhibition of NO synthesis (L-NAME, 10 µmol/L) induced a decrease in diameter in arteries submitted to pressure and flow (Figure 6) and did not affect arteries submitted to pressure only (1.5±2.0- to 2.1±2.2-µm change in diameter, n=7).
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Perfusion of angiotensin II (0.1 µmol/L) in mesenteric arteries after pretreatment of the vessel with losartan (10 µmol/L) induced a significant dilation (diameter from 90±3 to 108±4 µm, n=7, P<0.01). Angiotensin II–induced dilation was absent when the vessels were pretreated with losartan plus PD 123329 (10 µmol/L) (diameter from 104±6 to 102±7 µm, n=7, P=NS) or when the endothelium was disrupted in the presence of losartan (diameter from 84±9 to 88±11 µm, n=57, P=NS).
In mesenteric arteries isolated in an arteriograph, in vitro, flow induced a dilation (Figure 7) that was significantly less pronounced in vessels pretreated for 30 minutes with the AT2 receptor antagonist PD 123329 (1 µmol/L, Figure 7). In isolated mesenteric arteries pretreated with candesartan (0.1 µmol/L), the perfusion of angiotensin II (0.1 nmol/L) induced a significant dilation (Figure 8).
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RT–PCR of AT2 receptors revealed the presence of AT2 receptor mRNA (Figure 9), whereas Western blot analysis showed the presence of the AT2 receptors in the wall of mesenteric resistance arteries (Figure 10). Immunofluorescence analysis indicated that AT2 receptors are present in the endothelium of mesenteric resistance arteries (Figure 11).
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Discussion |
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The major new finding of the present study is that endogenous angiotensin II, through the activation of endothelial AT2 receptors, participated in flow-induced dilation in mesenteric resistance arteries in situ.
In resistance arteries, myogenic origin6 7 8 is counteracted by flow-induced dilation.3 5 6 7 8 9 The design of the experiments performed in the present study allowed us to measure a basal tone in the presence or in the absence of flow in 2 daughter arterial branches similar in size. In the branch distally ligated, only pressure was acting on the vessel wall, so that myogenic tone developed without opposition by flow-induced dilation. In the arterial branch submitted to both flow and pressure, myogenic tone was opposed by flow-induced dilation, so the resulting diameter was higher.
Blockade of AT2 receptors (PD 123319) decreased the diameter of the arteries submitted to pressure and flow but did not affect the diameter of the vessels ligated distally. Blockade of AT2 receptor blockers was concentration-dependent. In addition, because AT1 blockade had no effect on the diameter, we used saralasin (AT1 and AT2 blocker) to confirm the effect of PD 123319. Moreover, the dilation depending on the AT2 receptor stimulation by flow could be increased by the infusion of exogenous angiotensin II (in the presence of an AT1 receptor blocker) and could be reproduced in vitro. These observations suggest that locally produced angiotensin II participates in flow-induced dilation through AT2 receptor activation.
Previous studies support our observation that AT2 receptor activation might be involved in flow-induced dilation. Activation of AT2 receptors induces a dilation in cerebral arteries25 and in renal afferent arterioles.26 The AT2 receptors mediate cGMP production and NO synthesis.27 28 Also in support of our observation, it has been shown that AT2 receptor gene disruption increases blood pressure.29 30 Our results allow at least 2 possibilities to link shear stress and AT2-induced dilation: (1) flow might induce the local release of angiotensin II, which would activate AT2 receptors. This supposes that angiotensin II locally produced acts on endothelial cells only; or (2) flow might also allow a better diffusion of endogenous angiotensin II to its receptors. In agreement with the first possibility, a recent work has shown that short-term increases in shear stress enhance ACE activity.31 But in this case, angiotensin II produced should activate both AT1 and AT2 receptors, and AT2 receptor blockade had no effect in the present study. In support of the second possibility, it has been shown that flow increases the availability of agonists by influencing their mass transport.32 33 Nevertheless, the precise mechanism of AT2-dependent flow dilation remains to be elucidated. In the present study, AT2-dependent vasorelaxation represented a 10-µm increase in diameter. Such a change in a vascular tree might represent a considerable decrease in vascular resistance. In addition, AT2-dependent dilation represented 20% to 39% of the total flow-induced dilation (for shear stress values ranging from 22 to 37 dyn/cm2), obtained in vessels with a spontaneous tone mainly of myogenic origin. No exogenous drug was added. The presence of AT2 receptor and of its mRNA in the wall of mesenteric resistance arteries, evidenced by Western blot analysis, histoimmunofluorescence, and RT-PCR, is in agreement with a previous study performed in the same vessels.34 In addition, we provided evidence by immunofluorescence that AT2 receptors were present in the endothelium, which is in agreement with the pharmacological study described above.
Dilation induced by ACEIs in both branches (with or without flow) indicates that endogenous angiotensin II is released by the wall of small arteries in the presence or absence of flow. This result extends our previous studies, extending the vascular synthesis of angiotensin II participating in the local control of smooth muscle tone.12 13 14 ACE inhibition induced similar relaxation in the vessel submitted to flow and in the vessel not exposed to flow. This dilatation was in part reversed by bradykinin B2 receptor blockade. HOE 140 alone had no significant effect on the arterial diameter. These results are in agreement with previous studies showing that ACE inhibition induces a relaxation in part mediated by bradykinin, although in some vascular territories, it might not play an important role in basal tone.35
Thus, the present work shows that in rat resistance mesenteric arteries in situ, flow-induced dilation involves locally produced angiotensin II via endothelial AT2 receptor activation. Flow-induced AT2-dependent activation resulted in NO synthesis by the endothelium.
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Acknowledgments |
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This work was supported in part by a grant from IRIS (Servier, Paris, France). Khalid Matrougui was a fellow of the Recherche et Partage Foundation, Paris, France.
Received April 1, 1999; first decision May 18, 1999; accepted June 1, 1999.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Smiesko V, Johnson PC. The arterial lumen is controlled by flow-related shear stress. News Physiol Sci.. 1993;8:34–38.
2.
Davies PF. Flow-mediated endothelial
mechanotransduction. Physiol Rev.. 1995;75:519–559.
3.
Kuo L, William MC, Davis MJ. Interaction of
pressure- and flow-induced responses in porcine coronary
resistance vessels. Am J Physiol.. 1991;261:H1706–H1715.
4.
Koller A, Sun D, Kaley G. Role of shear stress and
endothelial prostaglandins in flow and
viscosity-induced dilation of arterioles in vitro. Circ Res.. 1993;72:1276–1284.
5.
Friebel M, Klotz KF, Ley K, Gaehtgens P, Pries A.
Flow-dependent regulation of arteriole diameter in rat skeletal muscle
in situ: role of endothelium-derived relaxing factor
and prostanoids. J Physiol.. 1995;483:715–726.
6. Bevan JA, Laher I. Pressure and flow-dependent vascular tone. FASEB J.. 1991;5:2267–2273.[Abstract]
7.
D'Angelo G, Meininger GA. Transduction mechanisms
involved in the regulation of myogenic activity.
Hypertension.. 1994;23:1096–1105.
8.
MacPherson RD, McLeod LJ, Rasiah RL. Myogenic response
of isolated pressurized rabbit ear artery is independent of
endothelium. Am J Physiol.. 1991;260:H779–H784.
9. Juncos LA, Garvin J, Carretero OA, Sadayoshi I. Flow modulates myogenic responses in isolated microperfused rabbit afferent arterioles via endothelium derived nitric oxide. J Clin Invest. 1995;95:2741–2748.
10.
Koller A, Huang A. Impaired nitric oxide-mediated
flow-induced dilatation in arterioles of spontaneously hypertensive
rats. Circ Res.. 1994;74:416–421.
11.
Matrougui K, Maclouf J, Levy BI, Henrion D. Impaired
nitric oxide– and prostaglandin-mediated responses to flow
in resistance arteries of hypertensive rats. Hypertension.. 1997;30:942–947.
12.
Caputo L, Tedgui A, Lévy BI. Control of carotid
vasomotor tone by local renin- angiotensin system in
normotensive and spontaneously hypertensive rats: role of
endothelium and flow. Circ Res.. 1995;77:303–309.
13.
Henrion D, Benessiano J, Lévy BI. In vitro
modulation of a resistance artery diameter by the tissue
renin-angiotensin system of a large donor artery.
Circ Res.. 1997;80:189–195.
14.
Qiu HY, Henrion D, Levy BI. Endogenous
angiotensin II enhances
phenylephrine-induced tone in hypertensive rats.
Hypertension.. 1994;24:317–321.
15.
Henrion D, Laher I, Laporte R, Bevan JA.
Angiotensin II amplifies arterial contractile
response to norepinephrine without increasing
45Ca2+ influx: role of
protein kinase C. J Pharmacol Exp Ther.. 1992;261:835–842.
16.
Caputo L, Benessiano J, Boulanger CM, Lévy BI.
Angiotensin II increases cGMP content via
endothelial angiotensin II
AT1 subtype receptor in the rat carotid artery.
Arterioscler Thromb Vasc Biol.. 1995;15:1646–1651.
17. Wiemer G, Schölkens BA, Busse R, Wagner A, Heitsch H, Linz W. The functional role of angiotensin II subtype AT2-receptors in endothelial cells and isolated ischemic rat hearts. Pharm Pharmacol Lett.. 1993;3:24–27.
18. Scheure DA, Perrone MH. Angiotensin II type 2 receptors mediated depressor phase of biphasic pressure response to angiotensin II. Am J Physiol.. 1993;33:R917–R923.
19.
Yamazaki T, Komuro I, Kudoh S, Zou Y, Shiojima I,
Mizuno T, Takano H, Hiroi Y, Ueki K, Tobe K. Angiotensin II
partly mediates mechanical stress-induced cardiac
hypertrophy. Circ Res.. 1995;77:258–265.
20. Sadishima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell.. 1993;75:977–984.[Medline] [Order article via Infotrieve]
21.
Bardy N, Karillon GJ, Merval R, Samuel JL, Tedgui A.
Differential effects of pressure and flow on DNA and protein synthesis
and on fibronectin expression by arteries in a novel organ culture
system. Circ Res.. 1995;77:684–694.
22. Henrion D, Terzi F, Matrougui K, Boulanger C, Duriez M, Boulanger C, Colucci-Guyon E, Babinet C, Briand P, Friedlander G, Poitevin P, Lévy BI. Impaired flow-induced dilation in mesenteric resistance arteries from mice lacking vimentin. J Clin Invest. 1997;100:2909–2914.[Medline] [Order article via Infotrieve]
23. Henrion D, Dechaux E, Dowell FJ, Maclouf J, Samuel JL, Lévy BI, Michel JB. Alteration of flow-induced dilation in mesenteric resistance arteries of L-NAME treated rats and its partial association with induction of cyclo-oxygenase-2. Br J Pharmacol.. 1997;121:83–90.[Medline] [Order article via Infotrieve]
24.
Matrougui K, Schiavi P, Guez D, Henrion D. High
sodium intake decreases pressure- induced (myogenic) tone and
flow-induced dilation in resistance arteries from hypertensive rats.
Hypertension.. 1998;32:176–179.
25.
Haberl RL, Anneser F, Villringer A,
Einhaupl KM. Angiotensin II induces
endothelium-dependent vasodilation of rat cerebral
arterioles. Am J Physiol.. 1990;258:H1840–H1846.
26. Arima S, Endo Y, Yaoita H, Omata K, Ogawa S, Tsunoda S, Abe M, Takeuch K, Abe K, Ito S. Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II in the isolated microperfused rabbit afferent arteriole. J Clin Invest.. 1997;100:2816–2823.[Medline] [Order article via Infotrieve]
27.
Gohlke P, Pees C, Unger T. AT2
receptor stimulation increases aortic cyclic GMP in SHRSP by a
kinin-dependent mechanism. Hypertension. 1998;31:349–355.
28. Siragy HM, Carey RM. The subtype-2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3',5'-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats. J Clin Invest.. 1996;97:1978–1982.[Medline] [Order article via Infotrieve]
29. Ichiki T, Labotsky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BLM, Inagami T. Effects on blood pressure and reduced exploratory behavior in mice lacking angiotensin II type 2 receptor. Nature.. 1995;377:748–750.[Medline] [Order article via Infotrieve]
30. Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature. 1995;377:744–747.[Medline] [Order article via Infotrieve]
31.
Rieder MJ, Carmona R, Krieger JE, Pritchard KA Jr,
Greene AS. Suppression of angiotensin-converting enzyme
expression and activity by shear stress. Circ Res.. 1997;80:312–319.
32.
Dull RO, Davies PF. Flow modulation of agonist (ATP)
response (Ca2+) coupling in vascular
endothelial cells. Am J Physiol.. 1991;261:H149–H156.
33.
Mo M, Eskin SG, Schilling WP. Flow-induced changes in
Ca2+ signaling of vascular
endothelial cells: effects of shear stress and ATP.
Am J Physiol.. 1991;260:H1698–H1707.
34.
Touyz RM, Endemann D, He G, Li JS, Schiffrin EL. Role
of AT2 receptors in angiotensin
II-stimulated contraction of small mesenteric arteries in young SHR.
Hypertension. 1999;33:366–372.
35. Linz W, Wiemer G, Gohlke P, Unger T, Schölkens BA. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Pharmacol Rev.. 1995;47:25–40.[Abstract]
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